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Luong TV, Cao MTT, Nguyen NVD, Dang HNN, Nguyen TT. Roles of autophagy and long non-coding RNAs in gastric cancer. World J Gastroenterol 2025; 31:101124. [PMID: 40124267 PMCID: PMC11924004 DOI: 10.3748/wjg.v31.i11.101124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 01/24/2025] [Accepted: 02/17/2025] [Indexed: 03/13/2025] Open
Abstract
Gastric cancer (GC) is one of the most aggressive malignancies worldwide and is characterized by its poor prognosis and resistance to conventional therapies. Autophagy and long non-coding RNAs (lncRNAs) play critical yet complex roles in GC, functioning as both tumor suppressors and promoters depending on the disease stage and context. Autophagy influences cellular homeostasis and metabolism, whereas lncRNAs regulate gene expression through epigenetic modifications, RNA sponging, and protein interactions. Notably, the interplay between lncRNAs and autophagy modulates tumor progression, metastasis, chemoresistance, and the tumor microenvironment. This study explored the intricate relationship between lncRNAs and autophagy in GC, highlighting their roles in pathogenesis and treatment resistance. By addressing current knowledge gaps and proposing innovative therapeutic strategies, we have emphasized the potential of targeting this dynamic interplay for improved diagnostic and therapeutic outcomes.
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Affiliation(s)
- Thang Viet Luong
- Department of Internal Medicine, University of Medicine and Pharmacy, Hue University, Hue 530000, Viet Nam
| | - Mai Thi Thu Cao
- Department of Biochemistry, University of Medicine and Pharmacy, Hue University, Hue 530000, Viet Nam
| | - Nam Van Duc Nguyen
- Department of Internal Medicine, University of Medicine and Pharmacy, Hue University, Hue 530000, Viet Nam
| | | | - Trung Tran Nguyen
- Department of Biotechnology, NTT Hi-Tech Institute, Nguyen Tat Thanh University, Ho Chi Minh City 700000, Viet Nam
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2
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Ren D, Zhao F, Li J, Guo X, Ma X, Zheng Y, Shen G, Zhao J. lncRNA TCONS_00251376 promotes the proliferation and migration of gastric cancer cell through upregulating ETV1. CANCER INNOVATION 2025; 4:e156. [PMID: 39668941 PMCID: PMC11636580 DOI: 10.1002/cai2.156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 04/15/2024] [Accepted: 04/22/2024] [Indexed: 12/14/2024]
Abstract
Background Although there have been significant advancements in the treatment modalities for gastric cancer (GC) in recent years, the overall prognosis remains poor, particularly for individuals in advanced stages. The absence of a sensitive tumor marker in GC is a crucial factor contributing to this challenge. Methods Our study focused on investigating a newly discovered long noncoding RNA (lncRNA) known as TCONS_00251376, which has been confirmed to exhibit differential expression in GC compared to adjacent tissues. To further validate these expression differences, we collected 22 pairs of GC and adjacent noncancerous tissues. Subsequent cell function experiments and animal studies were conducted to elucidate the role and underlying mechanisms of lncRNA TCONS_00251376 in the development of GC. Results The study revealed a significant upregulation of lncRNA TCONS_00251376 in cancer tissues (p < 0.01) and a consistent upregulation in GC cell lines (AGS, MKN45, BGC-823, and MGC-803). Furthermore, it was observed that lncRNA TCONS_00251376 played a promotive role in the proliferation, migration, and invasion of GC cells. Subsequent analysis indicated that lncRNA TCONS_00251376 could upregulate the expression of ETV1, a factor associated with the prognosis of GC. Conclusions Therefore, our findings suggest that lncRNA TCONS_00251376 functions as an oncogenic lncRNA, promoting tumorigenesis and progression by regulating the expression of ETV1 gene. This highlights its potential as an effective target for treating GC.
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Affiliation(s)
- Dengfeng Ren
- Breast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai UniversityXiningChina
- Qinghai Provincial Clinical Research Center for Cancer; Qinghai Provincial Institute of Cancer ResearchXiningChina
| | - Fuxing Zhao
- Breast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai UniversityXiningChina
- Qinghai Provincial Clinical Research Center for Cancer; Qinghai Provincial Institute of Cancer ResearchXiningChina
| | - Jinming Li
- Breast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai UniversityXiningChina
- Graduate School, Qinghai UniversityXiningChina
| | - Xinjian Guo
- Qinghai Provincial Clinical Research Center for Cancer; Qinghai Provincial Institute of Cancer ResearchXiningChina
- Department of PathologyAffiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai UniversityXiningChina
| | - Xinfu Ma
- Qinghai Provincial Clinical Research Center for Cancer; Qinghai Provincial Institute of Cancer ResearchXiningChina
- Department of Gastrointestinal Oncology SurgeryAffiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai UniversityXiningChina
| | - Yonghui Zheng
- Breast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai UniversityXiningChina
| | - Guoshuang Shen
- Breast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai UniversityXiningChina
- Qinghai Provincial Clinical Research Center for Cancer; Qinghai Provincial Institute of Cancer ResearchXiningChina
| | - Jiuda Zhao
- Breast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai UniversityXiningChina
- Qinghai Provincial Clinical Research Center for Cancer; Qinghai Provincial Institute of Cancer ResearchXiningChina
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3
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Sethi SC, Singh R, Sahay O, Barik GK, Kalita B. Unveiling the hidden gem: A review of long non-coding RNA NBAT-1 as an emerging tumor suppressor and prognostic biomarker in cancer. Cell Signal 2025; 126:111525. [PMID: 39592019 DOI: 10.1016/j.cellsig.2024.111525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 11/09/2024] [Accepted: 11/20/2024] [Indexed: 11/28/2024]
Abstract
Previously considered junk or non-functional, long non-coding RNAs (lncRNAs) have emerged over the past few decades as pivotal components in both physiological and pathological processes, including cancer. Neuroblastoma-associated transcript-1 (NBAT-1) was initially discovered a decade ago as a risk-associated tumor suppressor lncRNA in neuroblastoma (NB). Subsequent studies have consistently demonstrated that NBAT-1 serves as a dedicated tumor suppressor in many cancers. NBAT-1 is significantly downregulated in cancer, which is closely linked to higher histological grades, increased metastasis, and poor survival in cancer patients suggesting NBAT-1's potential as a prognostic biomarker. In this review, we delve into the current body of literature, elucidating the tumor-suppressive roles of NBAT-1 and the underlying regulatory mechanisms in the context of human malignancies. Additionally, we shed light on the mechanisms contributing to the diminished expression of NBAT-1 and its potential as both a prognostic biomarker and a promising therapeutic target in cancer.
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Affiliation(s)
- Subhash Chandra Sethi
- Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Ragini Singh
- Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Osheen Sahay
- Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
| | - Ganesh Kumar Barik
- Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
| | - Bhargab Kalita
- Amrita Research Center, Amrita Vishwa Vidyapeetham, Amrita Hospital, Mata Amritanandamayi Marg, Faridabad 121002, India.
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4
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Li BX, Wu MY, Wang ZH, Zhou DM, Li JQ, Lu BF, Lin XL, Zhao Y, Sheng XJ. Mechanism of hsa_circ_0069443 promoting early pregnancy loss through ALKBH5/FN1 axis in trophoblast cells. iScience 2025; 28:111608. [PMID: 39868042 PMCID: PMC11758834 DOI: 10.1016/j.isci.2024.111608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Revised: 06/30/2024] [Accepted: 12/12/2024] [Indexed: 01/28/2025] Open
Abstract
Studies have shown that circRNAs play an important regulatory role in trophoblast function and embryonic development. Based on sequencing and functional experiments, we found that hsa_circ_0069443 can regulate the function of trophoblast cells, and its presence is found in the exosomes secreted by trophoblast cells. It is known that exosomes mediate the interaction between the uterus and embryo, which is crucial for successful pregnancy. We found that trophoblast cell-derived exosomes overexpressing hsa_circ_0069443 promoted the migration and invasion of endometrial stromal cells as well as the EMT process of endometrial glandular epithelial cells, and this process promotes embryo implantation and adhesion, thus proving that a decrease in hsa_circ_0069443 may be the key factor leading to early pregnancy loss. This study also found that hsa_circ_0069443 can bind to the RNA-binding protein demethylase ALKBH5, affecting the overall m6A level of trophoblast cells, and hsa_circ_0069443 and ALKBH5 can regulate the expression level of FN1, verifying the role of the 0069443/ALKBH5/FN1 axis in trophoblast cells and endometrial stromal cells. In summary, this study demonstrates that hsa_circ_0069443 may be a key factor leading to early pregnancy loss, and the regulation of the hsa_circ_0069443/ALKBH5/FN1 axis may provide new insights into early diagnostic markers for early pregnancy loss.
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Affiliation(s)
- Bai-xue Li
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Department of Gynecologic Oncology Research Office, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangzhou Key Laboratory of Targeted Therapy for Gynecologic Oncology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine the Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
| | - Mei-yao Wu
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Department of Gynecologic Oncology Research Office, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangzhou Key Laboratory of Targeted Therapy for Gynecologic Oncology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Department of Gynecology, Queen Mary Hospital, Hong Kong, China
- Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine the Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
| | - Zhi-hui Wang
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Department of Gynecologic Oncology Research Office, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangzhou Key Laboratory of Targeted Therapy for Gynecologic Oncology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine the Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
| | - Dong-mei Zhou
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Department of Gynecologic Oncology Research Office, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangzhou Key Laboratory of Targeted Therapy for Gynecologic Oncology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine the Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
| | - Jian-qi Li
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Department of Gynecologic Oncology Research Office, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangzhou Key Laboratory of Targeted Therapy for Gynecologic Oncology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine the Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
| | - Bing-feng Lu
- Department of Gynecologic Oncology Research Office, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangzhou Key Laboratory of Targeted Therapy for Gynecologic Oncology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine the Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
| | - Xiao-ling Lin
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Department of Gynecologic Oncology Research Office, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangzhou Key Laboratory of Targeted Therapy for Gynecologic Oncology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine the Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
| | - Yang Zhao
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Department of Gynecologic Oncology Research Office, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangzhou Key Laboratory of Targeted Therapy for Gynecologic Oncology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine the Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
| | - Xiu-jie Sheng
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Department of Gynecologic Oncology Research Office, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangzhou Key Laboratory of Targeted Therapy for Gynecologic Oncology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
- Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine the Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
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Shi Y, Men X, Wang F, Li X, Zhang B. Role of long non-coding RNAs (lncRNAs) in gastric cancer metastasis: A comprehensive review. Pathol Res Pract 2024; 262:155484. [PMID: 39180802 DOI: 10.1016/j.prp.2024.155484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 07/17/2024] [Accepted: 07/22/2024] [Indexed: 08/27/2024]
Abstract
One of the greatest frequent types of malignancy is gastric cancer (GC). Metastasis, an essential feature of stomach cancer, results in a high rate of mortality and a poor prognosis. However, metastasis biological procedures are not well recognized. Long non-coding RNAs (lncRNAs) have a role in numerous gene regulation pathways via epigenetic modification as well as transcriptional and post-transcriptional control. LncRNAs have a role in a variety of disorders, such as cardiovascular disease, Alzheimer's, and cancer. LncRNAs are substantially related to GC incidence, progression, metastasis and drug resistance. Several research released information on the molecular processes of lncRNAs in GC pathogenesis. By interacting with a gene's promoter or enhancer region to influence gene expression, lncRNAs can operate as an oncogene or a tumor suppressor. This review includes the lncRNAs associated with metastasis of GC, which may give insights into the processes as well as potential clues for GC predicting and tracking.
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Affiliation(s)
- Yue Shi
- Department of Microbiology and Immunology, Changchun University of Chinese Medicine, Jilin 130117, PR China.
| | - Xiaoping Men
- Department of Clinical Laboratory, The First Affiliated Hospital to Changchun University of Chinese Medicine, Jilin 130021, PR China.
| | - Fang Wang
- Department of Microbiology and Immunology, Changchun University of Chinese Medicine, Jilin 130117, PR China.
| | - Xueting Li
- Experimental Center, Changchun University of Chinese Medicine, Jilin 130021, PR China.
| | - Biao Zhang
- School of Health Management, Changchun University of Chinese Medicine, Jilin 130117, PR China.
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Ahmadirad H, Pourghadamyari H, Hadizadeh M, Ali-Kheyl M, Eslami O, Afgar A, Sayadi AR, Mahmoodi M, Kesharwani P, Sahebkar A. Differential expression of long non-coding RNAs in colon cancer: Insights from transcriptomic analysis. Pathol Res Pract 2024; 261:155477. [PMID: 39067175 DOI: 10.1016/j.prp.2024.155477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 06/11/2024] [Accepted: 07/16/2024] [Indexed: 07/30/2024]
Abstract
BACKGROUND Colon Cancer (CC) incidence has sharply grown in recent years. Long non-coding RNAs (lncRNA) are produced by a group of non-protein-coding genes, and have important functions in controlling gene expression and impacting the biological features of various malignancies including CC. METHODS Our research focused on examining the function of lncRNAs in the development of colon cancer. To this end, we selected and analyzed a dataset (GSE104836) from the GEO database, which contained information about the expression of mRNAs and lncRNAs in both colon cancer tissues and normal adjacent paired tumor tissues. The DESeq2 R package in Bioconductor was used to identify differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) that showed differences in expression levels. Next, by literature review of previous studies, we chose two lncRNAs (FENDRR and LINC00092) for additional studies. To validate our findings, a series of tests were performed on a total of 31 tumor tissues and normal paired adjacent tumor tissues. The lncRNA expression levels were assessed in tumor tissues as well as in surrounding normal tumor tissues. RESULTS The data confirmed that just two particular lncRNAs, FENDRR and LINC00092, had considerably decreased expression levels throughout all stages of cancer. In addition, the survival assay was conducted using the GEPIA2 software, revealing that a reduced expression of FENDRR is correlated with a reduced overall survival. Furthermore, our investigation using receiver operating characteristic (ROC) methodology revealed that these two lncRNAs had significant discriminatory ability between colon cancer and normal tissues. To determine the cause of the decrease in the activity of these two long non-coding RNAs (lncRNAs), we used methylation-specific PCR (MSP) to examine the methylation pattern of their promoter regions. Our investigation revealed hypermethylation in the promoter regions of FENDRR and LINC00092 within tumor tissues compared to normal adjacent tumor tissues. CONCLUSION Taken together, our findings revealed the lncRNAs signatures as potential therapeutic targets and molecular diagnostic biomarkers in colon cancer. Furthermore, the evidence provided substantiates the important role of promoter methylation in regulating the expression levels for both of these lncRNAs.
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Affiliation(s)
- Hadis Ahmadirad
- Department of Clinical Biochemistry, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Hossein Pourghadamyari
- Department of Clinical Biochemistry, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran; Applied Cellular and Molecular Research Center, Kerman University of Medical Sciences, Kerman, Iran
| | - Morteza Hadizadeh
- Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
| | - Masoud Ali-Kheyl
- Department of Clinical Biochemistry, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Omid Eslami
- Gastroenterology and Hepatology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
| | - Ali Afgar
- Research Center for Hydatid Disease in Iran, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Ahmadreza Reza Sayadi
- Social Determinants of Health Research Center, Department of Psychiatric Nursing, School of Nursing and Midwifery, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Mehdi Mahmoodi
- Department of Clinical Biochemistry, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran; Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Science, Rafsanjan, Iran.
| | - Prashant Kesharwani
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India
| | - Amirhossein Sahebkar
- Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomeical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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7
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Kang Z, Wang C, Shao F, Deng H, Sun Y, Ren Z, Zhang W, Ding Z, Zhang J, Zang Y. The increase of long noncoding RNA Fendrr in hepatocytes contributes to liver fibrosis by promoting IL-6 production. J Biol Chem 2024; 300:107376. [PMID: 38762176 PMCID: PMC11190708 DOI: 10.1016/j.jbc.2024.107376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Revised: 04/14/2024] [Accepted: 05/07/2024] [Indexed: 05/20/2024] Open
Abstract
Liver fibrosis/cirrhosis is a pathological state caused by excessive extracellular matrix deposition. Sustained activation of hepatic stellate cells (HSC) is the predominant cause of liver fibrosis, but the detailed mechanism is far from clear. In this study, we found that long noncoding RNA Fendrr is exclusively increased in hepatocytes in the murine model of CCl4- and bile duct ligation-induced liver fibrosis, as well as in the biopsies of liver cirrhosis patients. In vivo, ectopic expression of Fendrr aggravated the severity of CCl4-induced liver fibrosis in mice. In contrast, inhibiting Fendrr blockaded the activation of HSC and ameliorated CCl4-induced liver fibrosis. Our mechanistic study showed that Fendrr binds to STAT2 and enhances its enrichment in the nucleus, which then promote the expression of interleukin 6 (IL-6), and, ultimately, activates HSC in a paracrine manner. Accordingly, disrupting the interaction between Fendrr and STAT2 by ectopic expression of a STAT2 mutant attenuated the profibrotic response inspired by Fendrr in the CCl4-induced liver fibrosis. Notably, the increase of Fendrr in patient fibrotic liver is positively correlated with the severity of fibrosis and the expression of IL-6. Meanwhile, hepatic IL-6 positively correlates with the extent of liver fibrosis and HSC activation as well, thus suggesting a causative role of Fendrr in HSC activation and liver fibrosis. In conclusion, these observations identify an important regulatory cross talk between hepatocyte Fendrr and HSC activation in the progression of liver fibrosis, which might represent a potential strategy for therapeutic intervention.
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Affiliation(s)
- Zhiqian Kang
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, PR China
| | - Chenqi Wang
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, PR China
| | - Fang Shao
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, PR China
| | - Hao Deng
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, PR China
| | - Yanyan Sun
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, PR China; State Key Laboratory for Organic Electronics and Information Displays (SKLOEID) & Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Jiangsu National Synergistic Innovation Center for Advanced Materials (SICAM), School of Chemistry and Life Sciences, Nanjing University of Posts and Telecommunications, Nanjing, PR China
| | - Zhengrong Ren
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, PR China
| | - Wei Zhang
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, PR China
| | - Zhi Ding
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, PR China
| | - Junfeng Zhang
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, PR China.
| | - Yuhui Zang
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, PR China.
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8
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Ghorbani A, Hosseinie F, Khorshid Sokhangouy S, Islampanah M, Khojasteh-Leylakoohi F, Maftooh M, Nassiri M, Hassanian SM, Ghayour-Mobarhan M, Ferns GA, Khazaei M, Nazari E, Avan A. The prognostic, diagnostic, and therapeutic impact of Long noncoding RNAs in gastric cancer. Cancer Genet 2024; 282-283:14-26. [PMID: 38157692 DOI: 10.1016/j.cancergen.2023.12.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Revised: 11/27/2023] [Accepted: 12/24/2023] [Indexed: 01/03/2024]
Abstract
Gastric cancer (GC), ranking as the third deadliest cancer globally, faces challenges of late diagnosis and limited treatment efficacy. Long non-coding RNAs (lncRNAs) emerge as valuable treasured targets for cancer prognosis, diagnosis, and therapy, given their high specificity, convenient non-invasive detection in body fluids, and crucial roles in diverse physiological and pathological processes. Research indicates the significant involvement of lncRNAs in various aspects of GC pathogenesis, including initiation, metastasis, and recurrence, underscoring their potential as novel diagnostic and prognostic biomarkers, as well as therapeutic targets for GC. Despite existing challenges in the clinical application of lncRNAs in GC, the evolving landscape of lncRNA molecular biology holds promise for advancing the survival and treatment outcomes of gastric cancer patients. This review provides insights into recent studies on lncRNAs in gastric cancer, elucidating their molecular mechanisms and exploring the potential clinical applications in GC.
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Affiliation(s)
- Atousa Ghorbani
- Department of Biology, East Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Fatemeh Hosseinie
- Department of Nursing, Faculty of Nursing and Midwifery, Mashhad Medical Sciences, Islamic Azad University, Mashhad, Iran
| | - Saeideh Khorshid Sokhangouy
- Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Muhammad Islampanah
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Mina Maftooh
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammadreza Nassiri
- Recombinant Proteins Research Group, The Research Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran
| | - Seyed Mahdi Hassanian
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Ghayour-Mobarhan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Gordon A Ferns
- Division of Medical Education, Brighton & Sussex Medical School, Falmer, Brighton, Sussex BN1 9PH, UK
| | - Majid Khazaei
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Elham Nazari
- Department of Health Information Technology and Management, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Amir Avan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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LI KUNLUN, LI DANDAN, HAFEZ BARBOD, BEKHIT MOUNIRMSALEM, JARDAN YOUSEFABIN, ALANAZI FARSKAED, TAHA EHABI, AUDA SAYEDH, RAMZAN FAIQAH, JAMIL MUHAMMAD. Identifying and validating MMP family members (MMP2, MMP9, MMP12, and MMP16) as therapeutic targets and biomarkers in kidney renal clear cell carcinoma (KIRC). Oncol Res 2024; 32:737-752. [PMID: 38560573 PMCID: PMC10972725 DOI: 10.32604/or.2023.042925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Accepted: 10/11/2023] [Indexed: 04/04/2024] Open
Abstract
Kidney Renal Clear Cell Carcinoma (KIRC) is a malignant tumor that carries a substantial risk of morbidity and mortality. The MMP family assumes a crucial role in tumor invasion and metastasis. This study aimed to uncover the mechanistic relevance of the MMP gene family as a therapeutic target and diagnostic biomarker in Kidney Renal Clear Cell Carcinoma (KIRC) through a comprehensive approach encompassing both computational and molecular analyses. STRING, Cytoscape, UALCAN, GEPIA, OncoDB, HPA, cBioPortal, GSEA, TIMER, ENCORI, DrugBank, targeted bisulfite sequencing (bisulfite-seq), conventional PCR, Sanger sequencing, and RT-qPCR based analyses were used in the present study to analyze MMP gene family members to accurately determine a few hub genes that can be utilized as both therapeutic targets and diagnostic biomarkers for KIRC. By performing STRING and Cytohubba analyses of the 24 MMP gene family members, MMP2 (matrix metallopeptidase 2), MMP9 (matrix metallopeptidase 9), MMP12 (matrix metallopeptidase 12), and MMP16 (matrix metallopeptidase 16) genes were denoted as hub genes having highest degree scores. After analyzing MMP2, MMP9, MMP12, and MMP16 via various TCGA databases and RT-qPCR technique across clinical samples and KIRC cell lines, interestingly, all these hub genes were found significantly overexpressed at mRNA and protein levels in KIRC samples relative to controls. The notable effect of the up-regulated MMP2, MMP9, MMP12, and MMP16 was also documented on the overall survival (OS) of the KIRC patients. Moreover, targeted bisulfite-sequencing (bisulfite-seq) analysis revealed that promoter hypomethylation pattern was associated with up-regulation of hub genes (MMP2, MMP9, MMP12, and MMP16). In addition to this, hub genes were involved in various diverse oncogenic pathways. The MMP gene family members (MMP2, MMP9, MMP12, and MMP16) may serve as therapeutic targets and prognostic biomarkers in KIRC.
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Affiliation(s)
- KUNLUN LI
- The Second Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, China
| | - DANDAN LI
- Department of Pharmaceutical Engineering, Jiangsu Ocean University, Lianyungang, China
| | - BARBOD HAFEZ
- Department of Biological Engineering, University of Salford, Salford, UK
| | - MOUNIR M. SALEM BEKHIT
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - YOUSEF A. BIN JARDAN
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - FARS KAED ALANAZI
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - EHAB I. TAHA
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - SAYED H. AUDA
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - FAIQAH RAMZAN
- Department of Animal and Poultry Production, Faculty of Veterinary and Animal Sciences, Gomal University, Dera Ismail Khan, Pakistan
| | - MUHAMMAD JAMIL
- Department of Arid Zone Research, PARC institute, Dera Ismail Khan, Pakistan
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10
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Chen C, Lin X, Tang Y, Sun H, Yin L, Luo Z, Wang S, Liang P, Jiang B. LncRNA Fendrr: involvement in the protective role of nucleolin against H 2O 2-induced injury in cardiomyocytes. Redox Rep 2023; 28:2168626. [PMID: 36719027 PMCID: PMC9891159 DOI: 10.1080/13510002.2023.2168626] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
Background: Nucleolin is a multifunctional nucleolar protein with RNA-binding properties. Increased nucleolin expression protects cells from H2O2-induced damage, but the mechanism remains unknown. Long noncoding RNAs (lncRNAs) play crucial roles in cardiovascular diseases. However, the biological functions and underlying mechanisms of lncRNAs in myocardial injury remain unclear.Methods: In a nucleolin-overexpressing cardiac cell line, high-throughput technology was used to identify lncRNAs controlled by nucleolin. Cell counting kit-8 assay was used to determine cell viability, lactate dehydrogenase (LDH) assay to detect cell death, caspase activity assay and propidium iodide staining to confirm cell apoptosis, and RNA immunoprecipitation to examine the interaction between Fendrr and nucleolin.Results: We found that Fendrr expression was significantly downregulated in mouse hearts subjected to myocardial ischemia-reperfusion (MI/R) injury. High Fendrr expression abrogated H2O2-mediated injury in cardiomyocytes as evidenced by increased cell viability and decreased cell apoptosis. Conversely, Fendrr knockdown exacerbated the cardiomyocytes injury. Also, nucleolin overexpression inhibits Fendrr downregulation in H2O2-induced cardiomyocyte injury. Fendrr overexpression significantly reversed the role of the suppression of nucleolin expression in H2O2-induced cardiomyocytes.Conclusion: LncRNA Fendrr is involved in the cardioprotective effect of nucleolin against H2O2-induced injury and may be a potential therapeutic target for oxidative stress-induced myocardial injury.
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Affiliation(s)
- Cheng Chen
- Department of Pathophysiology, Sepsis Translational Medicine Key Laboratory of Hunan Province, Xiangya School of Medicine, Central South University, Changsha, People’s Republic of China
| | - Xiaofang Lin
- Department of Pathophysiology, Sepsis Translational Medicine Key Laboratory of Hunan Province, Xiangya School of Medicine, Central South University, Changsha, People’s Republic of China
| | - Yuting Tang
- Department of Pathophysiology, Sepsis Translational Medicine Key Laboratory of Hunan Province, Xiangya School of Medicine, Central South University, Changsha, People’s Republic of China
| | - Hui Sun
- Department of Pathophysiology, Sepsis Translational Medicine Key Laboratory of Hunan Province, Xiangya School of Medicine, Central South University, Changsha, People’s Republic of China
| | - Leijing Yin
- Department of Pathophysiology, Sepsis Translational Medicine Key Laboratory of Hunan Province, Xiangya School of Medicine, Central South University, Changsha, People’s Republic of China
| | - Zhengyang Luo
- Department of Pathophysiology, Sepsis Translational Medicine Key Laboratory of Hunan Province, Xiangya School of Medicine, Central South University, Changsha, People’s Republic of China
| | - Shuxin Wang
- Department of Pathophysiology, Sepsis Translational Medicine Key Laboratory of Hunan Province, Xiangya School of Medicine, Central South University, Changsha, People’s Republic of China
| | - Pengfei Liang
- Department of Burns and Plastic Surgery, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
| | - Bimei Jiang
- Department of Pathophysiology, Sepsis Translational Medicine Key Laboratory of Hunan Province, Xiangya School of Medicine, Central South University, Changsha, People’s Republic of China
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11
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Wang S, Yang X, Liu C, Hu J, Yan M, Ding C, Fu Y. Identification of key genes associated with poor prognosis and neoplasm staging in gastric cancer. Medicine (Baltimore) 2023; 102:e35111. [PMID: 37800754 PMCID: PMC10553055 DOI: 10.1097/md.0000000000035111] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Accepted: 08/16/2023] [Indexed: 10/07/2023] Open
Abstract
BACKGROUND Gastric cancer (GC) is highly biologically and genetically heterogeneous disease with poor prognosis. Increasing evidence indicates that biomarkers can serve as prediction and clinical intervention. Therefore, it is vital to identify core molecules and pathways participating in the development of GC. METHODS In this study, GSE54129, GSE56807, GSE63089, and GSE118916 were used for identified overlapped 75 DEGs. GO and Kyoto Encyclopedia of Genes and Genomes pathway analysis showed DEGs mainly enriched in biological process about collagen-containing extracellular matrix and collagen metabolic. Next, protein-protein interaction network was built and the hub gene was excavated. Clinicopathological features and prognostic value were also evaluated. RESULTS Hub genes were shown as below, FN1, COL1A2, COL1A1, COL3A1, COL4A1, COL6A3, COL5A2, SPARC, PDGFRB, COL12A1. Those genes were upregulation in GC and related to the poor prognosis (except COL5A2, P = .73). What is more, high expression indicated worse T stage and tumor, node, metastasis stage in GC patients. Later, the results of 25 GC tumor specimens and 34 normal tissues showed that FN1, COL3A1, COL4A1, SPARC, COL5A2, and COL12A1 were significantly upregulated in cancer samples. CONCLUSION Our study systematically explored the core genes and crucial pathways in GC, providing insights into clinical management and individual treatment.
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Affiliation(s)
- Shuoshan Wang
- Department of General Medicine, The First People’s Hospital of Foshan, The Affiliated Foshan Hospital of Sun Yat-Sen University, Guangdong, China
| | - Xiansheng Yang
- Second Department of Gastrointestinal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, GuangZhou, China
| | - Chang Liu
- Guangzhou KingMed Center for Clinical Laboratory Co., Ltd, Guangzhou, China
| | - Jinlun Hu
- Department of General Medicine, The First People’s Hospital of Foshan, The Affiliated Foshan Hospital of Sun Yat-Sen University, Guangdong, China
| | - Mei Yan
- Department of General Medicine, The First People’s Hospital of Foshan, The Affiliated Foshan Hospital of Sun Yat-Sen University, Guangdong, China
| | - Chan Ding
- Department of General Medicine, The First People’s Hospital of Foshan, The Affiliated Foshan Hospital of Sun Yat-Sen University, Guangdong, China
| | - Yue Fu
- Department of General Medicine, The First People’s Hospital of Foshan, The Affiliated Foshan Hospital of Sun Yat-Sen University, Guangdong, China
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12
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Sun J, Li Q, Ding Y, Wei D, Hadisurya M, Luo Z, Gu Z, Chen B, Tao WA. Profiling Phosphoproteome Landscape in Circulating Extracellular Vesicles from Microliters of Biofluids through Functionally Tunable Paramagnetic Separation. Angew Chem Int Ed Engl 2023; 62:e202305668. [PMID: 37216424 PMCID: PMC11019431 DOI: 10.1002/anie.202305668] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Revised: 05/17/2023] [Accepted: 05/22/2023] [Indexed: 05/24/2023]
Abstract
Many biological processes are regulated through dynamic protein phosphorylation. Monitoring disease-relevant phosphorylation events in circulating biofluids is highly appealing but also technically challenging. We introduce here a functionally tunable material and a strategy, extracellular vesicles to phosphoproteins (EVTOP), which achieves one-pot extracellular vesicles (EVs) isolation, extraction, and digestion of EV proteins, and enrichment of phosphopeptides, with only a trace amount of starting biofluids. EVs are efficiently isolated by magnetic beads functionalized with TiIV ions and a membrane-penetrating peptide, octa-arginine R8 + , which also provides the hydrophilic surface to retain EV proteins during lysis. Subsequent on-bead digestion concurrently converts EVTOP to TiIV ion-only surface for efficient enrichment of phosphopeptides for phosphoproteomic analyses. The streamlined, ultra-sensitive platform enabled us to quantify 500 unique EV phosphopeptides with only a few μL of plasma and over 1200 phosphopeptides with 100 μL of cerebrospinal fluid (CSF). We explored its clinical application of monitoring the outcome of chemotherapy of primary central nervous system lymphoma (PCNSL) patients with a small volume of CSF, presenting a powerful tool for broad clinical applications.
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Affiliation(s)
- Jie Sun
- State Key Laboratory of Bioelectronics, National Demonstration Center for Experimental Biomedical Engineering Education, Southeast University, Nanjing, China
| | - Qing Li
- Department of Hematology, Huashan Hospital, Shanghai, China
| | - Yajie Ding
- State Key Laboratory of Bioelectronics, National Demonstration Center for Experimental Biomedical Engineering Education, Southeast University, Nanjing, China
| | - Dong Wei
- State Key Laboratory of Bioelectronics, National Demonstration Center for Experimental Biomedical Engineering Education, Southeast University, Nanjing, China
| | - Marco Hadisurya
- Department of Biochemistry, Department of Biochemistry, Purdue University, West Lafayette, IN 47907; Institute for Cancer ResearchPurdue University West Lafayette, IN47907
| | - Zhuojun Luo
- Department of Biochemistry, Department of Biochemistry, Purdue University, West Lafayette, IN 47907; Institute for Cancer ResearchPurdue University West Lafayette, IN47907
| | - Zhongze Gu
- State Key Laboratory of Bioelectronics, National Demonstration Center for Experimental Biomedical Engineering Education, Southeast University, Nanjing, China
| | - Bobin Chen
- Department of Hematology, Huashan Hospital, Shanghai, China
| | - W. Andy Tao
- Department of Biochemistry, Department of Biochemistry, Purdue University, West Lafayette, IN 47907; Institute for Cancer ResearchPurdue University West Lafayette, IN47907
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13
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Fazaeli H, Sheikholeslami A, Ghasemian F, Amini E, Sheykhhasan M. The Emerging Role of LncRNA FENDRR in Multiple Cancers: A Review. Curr Mol Med 2023; 23:606-629. [PMID: 35579154 DOI: 10.2174/1566524022666220509122505] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Revised: 01/18/2022] [Accepted: 01/19/2022] [Indexed: 11/22/2022]
Abstract
Long noncoding RNAs (lncRNAs) are prominent as crucial regulators of tumor establishment and are repeatedly dysregulated in multiple cancers. Therefore, lncRNAs have been identified to play an essential function in carcinogenesis and progression of cancer at genetic and epigenetic levels. FENDRR (fetal-lethal noncoding developmental regulatory RNA) as a LncRNA is a hallmark of various malignancies. FENDRR is crucial for multiple organs' development, such as the lung and heart. The effects of FENDRR under signaling pathways in different cancers have been identified. In addition, it has been verified that FENDRR can affect the development and progression of various cancers. In addition, FENDRR expression has been associated with epigenetic regulation of target genes participating in tumor immunity. Furthermore, FENDRR downregulation was observed in various types of cancers, including colorectal cancer, gastric cancer, pancreatic cancer, cholangiocarcinoma, liver cancer, gallbladder cancer, lung cancer, breast cancer, endometrial cancer, prostate cancer, chronic myeloid leukemia, osteosarcoma, and cutaneous malignant melanoma cells. Here, we review the biological functions and molecular mechanisms of FENDRR in several cancers, and we will discuss its potential as a cancer biomarker and as a probable option for cancer treatment.
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Affiliation(s)
- Hoda Fazaeli
- Department of Mesenchymal Stem Cells, Academic Center for Education, Culture and Research (ACECR), Qom Branch, Qom, Iran
| | - Azar Sheikholeslami
- Department of Mesenchymal Stem Cells, Academic Center for Education, Culture and Research (ACECR), Qom Branch, Qom, Iran
| | - Fatemeh Ghasemian
- Department of Biology, Faculty of Science, University of Guilan, Rasht, Iran
| | - Elaheh Amini
- Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran
| | - Mohsen Sheykhhasan
- Department of Mesenchymal Stem Cells, Academic Center for Education, Culture and Research (ACECR), Qom Branch, Qom, Iran
- Department of Molecular Medicine and Genetics, Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
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14
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Sun S, Zou Y, Xu N, Wang K, Rong S, Lv J, Hu B, Mai Y, Zhu D, Ding L. Long non-coding RNA ATB expedites non-small cell lung cancer progression by the miR-200b/fibronectin 1 axis. J Clin Lab Anal 2023; 37:e24822. [PMID: 36806318 PMCID: PMC10020841 DOI: 10.1002/jcla.24822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 11/05/2022] [Accepted: 11/07/2022] [Indexed: 02/22/2023] Open
Abstract
BACKGROUND Long non-coding RNA (lncRNA) ATB belongs to an active modulator in multiple cancers, but its expression along with potential underlying non-small cell lung cancer (NSCLC) is obscure. Our study aimed to investigate the role and potential mechanism of LncRNA ATB in NSCLC. METHODS LncRNA ATB expression in NSCLC tissues and cell lines was detected by qRT-PCR. Effects of LncRNA ATB on NSCLC cell proliferation, migration and invasion were assessed by MTS, colony formation and transwell assays. The connection among LncRNA ATB, miR-200b and fibronectin 1 (FN1) was determined by bioformatics prediction and luciferase reporter assay. RESULTS In this research, upregulation of LncRNA ATB was discovered in NSCLC tissue samples and cell lines. LncRNA ATB was positively related to advanced tumor phase as well as lymph node metastasis. Cell function assays reflected LncRNA ATB expedited NSCLC cells proliferation, migration and invasion. LncRNA ATB promoted fibronectin 1 (FN1) expression via inhibiting miR-200b. Furthermore, LncRNA ATB depletion suppressed NSCLC cells proliferation, migration and invasion, while miR-200b inhibitor or pcDNA-FN1 rescued these effects. CONCLUSION In summary, our outcomes elucidated that LncRNA ATB/miR-200b axis expedited NSCLC cells proliferation, migration and invasion by up-regulating FN1.
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Affiliation(s)
- Shifang Sun
- Department of Geriatrics MedicineThe Affiliated Hospital of Medical School of Ningbo UniversityNingboChina
| | - Yifan Zou
- Department of Geriatrics MedicineThe Affiliated Hospital of Medical School of Ningbo UniversityNingboChina
| | - Ningjie Xu
- School of MedicineNingbo UniversityNingboChina
| | - Kaiyue Wang
- Department of Geriatrics MedicineThe Affiliated Hospital of Medical School of Ningbo UniversityNingboChina
| | - Shanshan Rong
- Department of Geriatrics MedicineThe Affiliated Hospital of Medical School of Ningbo UniversityNingboChina
| | - Jiarong Lv
- Department of Geriatrics MedicineThe Affiliated Hospital of Medical School of Ningbo UniversityNingboChina
| | - Bin Hu
- School of MedicineNingbo UniversityNingboChina
| | - Yifeng Mai
- Department of Geriatrics MedicineThe Affiliated Hospital of Medical School of Ningbo UniversityNingboChina
| | - Decai Zhu
- Department of Geriatrics MedicineThe Affiliated Hospital of Medical School of Ningbo UniversityNingboChina
| | - Liren Ding
- Department of Respiratory and Critical Care MedicineThe Second Affiliated Hospital of Zhejiang University Medical CollegeHangzhouChina
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15
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Aydın E, Saus E, Chorostecki U, Gabaldón T. A hybrid approach to assess the structural impact of long noncoding RNA mutations uncovers key
NEAT1
interactions in colorectal cancer. IUBMB Life 2023. [PMID: 36971476 DOI: 10.1002/iub.2710] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Accepted: 01/25/2023] [Indexed: 03/29/2023]
Abstract
Long noncoding RNAs (lncRNAs) are emerging players in cancer and they entail potential as prognostic biomarkers or therapeutic targets. Earlier studies have identified somatic mutations in lncRNAs that are associated with tumor relapse after therapy, but the underlying mechanisms behind these associations remain unknown. Given the relevance of secondary structure for the function of some lncRNAs, some of these mutations may have a functional impact through structural disturbance. Here, we examined the potential structural and functional impact of a novel A > G point mutation in NEAT1 that has been recurrently observed in tumors of colorectal cancer patients experiencing relapse after treatment. Here, we used the nextPARS structural probing approach to provide first empirical evidence that this mutation alters NEAT1 structure. We further evaluated the potential effects of this structural alteration using computational tools and found that this mutation likely alters the binding propensities of several NEAT1-interacting miRNAs. Differential expression analysis on these miRNA networks shows upregulation of Vimentin, consistent with previous findings. We propose a hybrid pipeline that can be used to explore the potential functional effects of lncRNA somatic mutations.
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Affiliation(s)
- Efe Aydın
- Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, Lund, Sweden
| | - Ester Saus
- Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain
- Barcelona Supercomputing Centre (BSC-CNS). Plaça Eusebi Güell, Barcelona, Spain
| | - Uciel Chorostecki
- Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain
- Barcelona Supercomputing Centre (BSC-CNS). Plaça Eusebi Güell, Barcelona, Spain
| | - Toni Gabaldón
- Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain
- Barcelona Supercomputing Centre (BSC-CNS). Plaça Eusebi Güell, Barcelona, Spain
- Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain
- Centro de Investigación Biomédica En Red de Enfermedades Infecciosas (CIBERINFEC), Barcelona, Spain
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16
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Ranjbar M, Heydarzadeh S, Shekari Khaniani M, Foruzandeh Z, Seif F, Pornour M, Rahmanpour D, Tarhriz V, Alivand M. Mutual interaction of lncRNAs and epigenetics: focusing on cancer. EGYPTIAN JOURNAL OF MEDICAL HUMAN GENETICS 2023. [DOI: 10.1186/s43042-023-00404-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/08/2023] Open
Abstract
AbstractLong noncoding RNAs are characterized as noncoding transcripts longer than 200 nucleotides in response to a variety of functions within the cells. They are involved in almost all cellular mechanisms so as epigenetics. Given that epigenetics is an important phenomenon, which participates in the biology of complex diseases, many valuable studies have been performed to demonstrate the control status of lncRNAs and epigenetics. DNA methylation and histone modifications as epigenetic mechanisms can regulate the expression of lncRNAs by affecting their coding genes. Reciprocally, the three-dimensional structure of lncRNAs could mechanistically control the activity of epigenetic-related enzymes. Dysregulation in the mutual interaction between epigenetics and lncRNAs is one of the hallmarks of cancer. These mechanisms are either directly or indirectly involved in various cancer properties such as proliferation, apoptosis, invasion, and metastasis. For instance, lncRNA HOTAIR plays a role in regulating the expression of many genes by interacting with epigenetic factors such as DNA methyltransferases and EZH2, and thus plays a role in the initiation and progression of various cancers. Conversely, the expression of this lncRNA is also controlled by epigenetic factors. Therefore, focusing on this reciprocated interaction can apply to cancer management and the identification of prognostic, diagnostic, and druggable targets. In the current review, we discuss the reciprocal relationship between lncRNAs and epigenetic mechanisms to promote or prevent cancer progression and find new potent biomarkers and targets for cancer diagnosis and therapy.
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17
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Xu X, Duan F, Ng S, Wang H, Wang K, Li Y, Niu G, Xu E. Clinicopathological and prognostic value of lncRNAs expression in gastric cancer: A field synopsis of observational studies and databases validation. Medicine (Baltimore) 2022; 101:e30817. [PMID: 36221326 PMCID: PMC9543081 DOI: 10.1097/md.0000000000030817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 08/30/2022] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND The purpose of this study was to evaluate existing evidence in the field of long non-coding RNAs (lncRNAs) and prognosis of gastric cancer. METHODS A comprehensive literature search was performed through the electronic database. The combined hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of overall survival (OS), disease-free survival (DFS), or progression free survival (PFS) were calculated to assess the strength of the association. Kaplan-Meier (KM) plotter was used to verify lncRNA HOX transcript antisense RNA (HOTAIR) expression and OS. RESULTS Overall, a significant correlation between high lncRNAs expression and poor OS was explored in patients with gastric cancer (HR = 1.78, P < .001). Subgroup analysis based on statistical methods indicated the high expression of lncRNAs in log-rank (HR = 1.87, P < .001) and multivariate analysis (HR = 1.71, P < .001) were all significantly correlated with the poor OS. Clinicopathological parameters analysis showed the lncRNA expression were significantly associated prognosis, including TNM stage, tumor size, pathological differentiation, lymph nodes metastasis, distance metastasis, invasion depth and Lauren's classification. It was consistent with the verification results of bioinformatics database for lncRNA HOTAIR (P < .001). CONCLUSION Our study confirmed the expression of lncRNAs and clinicopathological features may serve as effective indicators of prognosis in patients with gastric cancer.
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Affiliation(s)
- Xiaona Xu
- School of Traditional Chinese Medicine (Zhongjing College), Henan University of Traditional Chinese Medicine, Zhengzhou, China
| | - Fujiao Duan
- Department of Hematology and Medical Research Office, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Key Laboratory of Tumor Epidemiology of Henan Province, Zhengzhou, Henan Province, China
| | - Shiutin Ng
- The First Clinical Medical College of Henan University of Traditional Chinese Medicine, Zhengzhou, China
| | - Haili Wang
- School of Traditional Chinese Medicine (Zhongjing College), Henan University of Traditional Chinese Medicine, Zhengzhou, China
| | - Kaijuan Wang
- Key Laboratory of Tumor Epidemiology of Henan Province, Zhengzhou, Henan Province, China
- College of Public Health, Zhengzhou University, Zhengzhou, Henan Province, China
| | - Yilin Li
- Department of Hematology and Medical Research Office, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Guanghui Niu
- Department of Hematology and Medical Research Office, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Erping Xu
- School of Traditional Chinese Medicine (Zhongjing College), Henan University of Traditional Chinese Medicine, Zhengzhou, China
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18
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Tan X, Liu Z, Wang Y, Wu Z, Zou Y, Luo S, Tang Y, Chen D, Yuan G, Yao K. miR-138-5p-mediated HOXD11 promotes cell invasion and metastasis by activating the FN1/MMP2/MMP9 pathway and predicts poor prognosis in penile squamous cell carcinoma. Cell Death Dis 2022; 13:816. [PMID: 36151071 PMCID: PMC9508180 DOI: 10.1038/s41419-022-05261-2] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Revised: 09/07/2022] [Accepted: 09/12/2022] [Indexed: 01/23/2023]
Abstract
The presence and extent of regional lymph node and distant metastasis are the most fatal prognostic factors in penile squamous cell carcinoma (PSCC). However, the available biomarkers and detailed mechanisms underlying the metastasis of PSCC remain elusive. Here, we explored the expression landscape of HOX genes in twelve paired PSCC tissues, including primary tumors, metastatic lymph nodes and corresponding normal tissues, and highlighted that HOXD11 was indispensable in the progression of PSCC. HOXD11 was upregulated in PSCC cell lines and tumors, especially in metastatic lymph nodes. High HOXD11 expression was associated with aggressive features, such as advanced pN stages, extranodal extension, pelvic lymph node and distant metastasis, and predicted poor survival. Furthermore, tumorigenesis assays demonstrated that knockdown of HOXD11 not only inhibited the capability of cell proliferation, invasion and tumor growth but also reduced the burden of metastatic lymph nodes. Further mechanistic studies indicated that miR-138-5p was a tumor suppressor in PSCC by inhibiting the translation of HOXD11 post-transcriptionally through binding to the 3' untranslated region. Furthermore, HOXD11 activated the transcription of FN1 to decompose the extracellular matrix and to promote epithelial mesenchymal transition-like phenotype metastasis via FN1/MMP2/MMP9 pathways. Our study revealed that HOXD11 is a promising prognostic biomarker and predicts advanced disease with poor outcomes, which could serve as a potential therapeutic target for PSCC.
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Affiliation(s)
- Xingliang Tan
- grid.488530.20000 0004 1803 6191Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China ,grid.12981.330000 0001 2360 039XState Key Laboratory of Oncology in Southern China, Guangzhou, China ,grid.488530.20000 0004 1803 6191Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
| | - Zhenhua Liu
- grid.488530.20000 0004 1803 6191Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China ,grid.12981.330000 0001 2360 039XState Key Laboratory of Oncology in Southern China, Guangzhou, China ,grid.488530.20000 0004 1803 6191Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
| | - Yanjun Wang
- grid.488530.20000 0004 1803 6191Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China ,grid.12981.330000 0001 2360 039XState Key Laboratory of Oncology in Southern China, Guangzhou, China ,grid.488530.20000 0004 1803 6191Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
| | - Zhiming Wu
- grid.488530.20000 0004 1803 6191Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China ,grid.12981.330000 0001 2360 039XState Key Laboratory of Oncology in Southern China, Guangzhou, China ,grid.488530.20000 0004 1803 6191Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
| | - Yuantao Zou
- grid.488530.20000 0004 1803 6191Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China ,grid.12981.330000 0001 2360 039XState Key Laboratory of Oncology in Southern China, Guangzhou, China ,grid.488530.20000 0004 1803 6191Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
| | - Sihao Luo
- grid.488530.20000 0004 1803 6191Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China ,grid.12981.330000 0001 2360 039XState Key Laboratory of Oncology in Southern China, Guangzhou, China ,grid.488530.20000 0004 1803 6191Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
| | - Yi Tang
- grid.488530.20000 0004 1803 6191Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China ,grid.12981.330000 0001 2360 039XState Key Laboratory of Oncology in Southern China, Guangzhou, China ,grid.488530.20000 0004 1803 6191Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
| | - Dong Chen
- grid.488530.20000 0004 1803 6191Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China ,grid.12981.330000 0001 2360 039XState Key Laboratory of Oncology in Southern China, Guangzhou, China ,grid.488530.20000 0004 1803 6191Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
| | - Gangjun Yuan
- grid.190737.b0000 0001 0154 0904Department of Urology Oncological Surgery, Chongqing University Cancer Hospital, Chongqing, China ,grid.190737.b0000 0001 0154 0904Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, China
| | - Kai Yao
- grid.488530.20000 0004 1803 6191Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China ,grid.12981.330000 0001 2360 039XState Key Laboratory of Oncology in Southern China, Guangzhou, China ,grid.488530.20000 0004 1803 6191Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
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Establishment and Analysis of a Prognostic Model of Autophagy-Related lncRNAs in ESCA. BIOMED RESEARCH INTERNATIONAL 2022; 2022:9265088. [PMID: 35928921 PMCID: PMC9345713 DOI: 10.1155/2022/9265088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 07/07/2022] [Indexed: 12/05/2022]
Abstract
Esophageal cancer (ESCA) is a malignant tumor of the upper gastrointestinal tract, with a high mortality rate and poor prognosis. Long noncoding RNAs (lncRNAs) play a role in the malignant progression of tumors by regulating autophagy. This study is aimed at establishing a prognostic model of autophagy-related lncRNAs in ESCA and provide a theoretical basis to determine potential therapeutic targets for ESCA. The transcriptome expression profiles were downloaded from The Cancer Genome Atlas (TCGA). We identified autophagy-related mRNAs and lncRNAs in ESCA using differential expression analysis and the Human Autophagy Database (HADb). Four differentially expressed autophagy-related lncRNAs with a prognostic value were identified using Cox regression and survival analyses. Furthermore, the combination of the selected lncRNAs was able to predict the prognosis of patients with ESCA more accurately than any of the four lncRNAs individually. Finally, we constructed a coexpression network of autophagy-related mRNAs and lncRNAs. This study showed that autophagy-related lncRNAs play an important role in the occurrence and development of ESCA and could become a new target for the diagnosis and treatment of this disease.
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20
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Chen B, Wang T, Zhang J, Zhang S, Shang X. Identification of Colon Cancer-Related RNAs Based on Heterogeneous Networks and Random Walk. BIOLOGY 2022; 11:1003. [PMID: 36101384 PMCID: PMC9312154 DOI: 10.3390/biology11071003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Revised: 06/25/2022] [Accepted: 06/28/2022] [Indexed: 11/17/2022]
Abstract
Colon cancer is considered as a complex disease that consists of metastatic seeding in early stages. Such disease is not simply caused by the action of a single RNA, but is associated with disorders of many kinds of RNAs and their regulation relationships. Hence, it is of great significance to study the complex regulatory roles among mRNAs, miRNAs and lncRNAs for further understanding the pathogenic mechanism of colon cancer. In this study, we constructed a heterogeneous network consisting of differentially expressed mRNAs, miRNAs and lncRNAs. This contains three kinds of vertices and six types of edges. All RNAs were re-divided into three categories, which were "related", "irrelevant" and "unlabeled". They were processed by dynamic excitation restart random walk (RW-DIR) for identifying colon cancer-related RNAs. Ten RNAs were finally obtained related to colon cancer, which were hsa-miR-2682-5p, hsa-miR-1277-3p, ANGPTL1, SLC22A18AS, FENDRR, PHLPP2, hsa-miR-302a-5p, APCDD1, MEX3A and hsa-miR-509-3-5p. Numerical experiments have indicated that the proposed network construction framework and the following RW-DIR algorithm are effective for identifying colon cancer-related RNAs, and this kind of analysis framework can also be easily extended to other diseases, effectively narrowing the scope of biological experimental research.
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Affiliation(s)
- Bolin Chen
- School of Computer Science, Northwestern Polytechnical University, Xi’an 710072, China; (B.C.); (T.W.); (J.Z.)
| | - Teng Wang
- School of Computer Science, Northwestern Polytechnical University, Xi’an 710072, China; (B.C.); (T.W.); (J.Z.)
| | - Jinlei Zhang
- School of Computer Science, Northwestern Polytechnical University, Xi’an 710072, China; (B.C.); (T.W.); (J.Z.)
| | - Shengli Zhang
- School of Information Technology, Minzu Normal University of Xingyi, Xingyi 562400, China;
| | - Xuequn Shang
- School of Computer Science, Northwestern Polytechnical University, Xi’an 710072, China; (B.C.); (T.W.); (J.Z.)
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21
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She Q, Chen Y, Liu H, Tan J, Li Y. A high level of the long non-coding RNA MCF2L-AS1 is associated with poor prognosis in breast cancer and MCF2L-AS1 activates YAP transcriptional activity to enhance breast cancer proliferation and metastasis. Bioengineered 2022; 13:13437-13451. [PMID: 36700469 PMCID: PMC9276029 DOI: 10.1080/21655979.2022.2074108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
Breast cancer (BC) is one of the most prevalent gynecologic malignant tumors with a poor prognosis and the second leading cause of cancer-related deaths in women worldwide. In recent years, it has been shown that long non-coding RNA (lncRNA) plays an important role in the development of breast cancer (BC). An antisense lncRNA from the MCF2 cell line (MCF2L-AS1) has been discovered recently and has been shown to function in a variety of malignancies. However, its function as a regulator of BC development has yet to be determined. Herein, the bioinformatics study analysis showed that MCF2L-AS1 was frequently highly expressed in BC tumors, and this overexpression was associated with worse patient outcomes. BC cells' proliferation, migration, and invasion are inhibited when MCF2L-AS1 is silenced, whereas the inverse is evident when MCF2L-AS1 is overexpressed. It was also observed that MCF2L-AS1 knockdown decreased carcinogenesis in xenograft tumor models. Furthermore, we discovered that MCF2L-AS1 could bind to and improve the transcription activity of the yes-associated protein (YAP). However, following YAP knockdown, this lncRNA's ability to drive BC malignancy was considerably reduced. In conclusion, MCF2L-AS1 may represent a potential predictive biomarker in BC patients, as well as a key regulator of BC cell proliferation. It works through positive feedback processes involving direct YAP binding and subsequent modulation of intracellular gene expression. Our findings add to our understanding of MCF2L-AS1 regulation and its potential as a therapeutic target in patients with this fatal cancer type.
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Affiliation(s)
- Qing She
- Department of Breast Surgery, Baoji Municipal Central Hospital, Baoji, China
| | - Yuanyuan Chen
- Department of Breast Surgery, Baoji Municipal Central Hospital, Baoji, China
| | - Hong Liu
- Department of Breast Surgery, Baoji Municipal Central Hospital, Baoji, China
| | - Jichao Tan
- Department of Breast Surgery, Baoji Municipal Central Hospital, Baoji, China
| | - Youhuai Li
- Department of Breast Surgery, Baoji Municipal Central Hospital, Baoji, China,CONTACT Youhuai Li Department of Breast Surgery, Baoji Municipal Central Hospital, 8 Jiangtan Road, Weibin District, Baoji, Shaanxi721008, China
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22
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Wang W, Pei Q, Wang L, Mu T, Feng H. Construction of a Prognostic Signature of 10 Autophagy-Related lncRNAs in Gastric Cancer. Int J Gen Med 2022; 15:3699-3710. [PMID: 35411177 PMCID: PMC8994655 DOI: 10.2147/ijgm.s348943] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Accepted: 02/25/2022] [Indexed: 12/12/2022] Open
Abstract
Background Autophagy plays a double-edged sword role in cancers. LncRNAs could regulate cancer initiation and development at various levels. However, the role of autophagy-related lncRNAs (ARlncs) in gastric cancer (GC) remains indistinct. Methods GC gene expression profile and clinical data were acquired from the Cancer Genome Atlas (TCGA). The prognostic signature composed of ARlncs was established via cox regression analysis. Kaplan–Meier (K-M) survival curve was adopted to show overall survival (OS). Independence and reliability of risk signature were visualized by cox regression analysis and ROC curve. A nomogram was constructed and the reliability was analyzed by ROC curve. Immune infiltrating cells and check points were also analyzed. Results A prognostic signature was constructed which stratified GC patients into high- and low-risk groups according to risk score calculated via the 10 ARlncs including LINC01094, AC068790.7, AC090772.1, AC005165.1, PVT1, LINC00106, AC026368.1, AC090912.3, AC013652.1, UICLM. Patients in high-risk group showed a poor prognosis (p<0.001). Cox regression analysis showed signature was an independent prognostic factor (p<0.001). Areas under curves (AUC) of ROC for risk signature for predicting OS outweighed age, gender, grade, T, M and N, which suggested the reliability of the signature. A nomogram was constructed with risk signature, T, M, N and age and its AUC of ROC for 1-, 3-, and 5-year was 0.700, 0.730, 0.757 respectively, which showed good reliability. Macrophage M2, T cell CD8+ and T cell CD4+ memory resting had greatest difference between the two risk groups according to CIBERSORE-ABS algorithm (p<0.001). CD274 (PD-L1), PDCD1 (PD-1) and PDCD1LG2 (PD-L2) were expressed higher in the high-risk group (p<0.05), which implied that immunotherapy may be a good choice for these patients. Conclusion The risk signature based on 10 ARlncs can serve as an efficacious prognostic predictor and guide the immunotherapies and precise treatment for GC patients.
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Affiliation(s)
- Wenwen Wang
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China
- Shandong Provincial Engineering and Technological Research Center for Liver Diseases Prevention and Control, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China
| | - Qingshan Pei
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China
| | - Lifen Wang
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China
| | - Tong Mu
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China
| | - Hua Feng
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China
- Correspondence: Hua Feng, Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jing 5 Road, Jinan, Shandong, 250021, People’s Republic of China, Tel +86 531-68773293, Fax +86 531-87906348, Email
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23
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Xu Y, Lin G, Liu Y, Lin X, Lin H, Guo Z, Xu Y, Lin Q, Chen S, Yang J, Zeng Y. An integrated analysis of the competing endogenous RNA network associated of prognosis of stage I lung adenocarcinoma. BMC Cancer 2022; 22:188. [PMID: 35183135 PMCID: PMC8857797 DOI: 10.1186/s12885-022-09290-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 02/08/2022] [Indexed: 12/25/2022] Open
Abstract
Abstract
Background
Accumulating evidence indicates that long non-coding RNAs (lncRNAs) are involving in the tumorigenesis and metastasis of lung cancer. The aim of the study is to systematically characterize the lncRNA-associated competing endogenous RNA (ceRNA) network and identify key lncRNAs in the development of stage I lung adenocarcinoma (LUAD).
Methods
Totally, 1,955 DEmRNAs, 165 DEmiRNAs and 1,107 DElncRNAs were obtained in 10 paired normal and LUAD tissues. And a total of 8,912 paired lncRNA-miRNA-mRNA network was constructed. Using the Cancer Genome Atlas (TCGA) dataset, the module of ME turquoise was revealed to be most relevant to the progression of LUAD though Weighted Gene Co-expression Network Analysis (WGCNA).
Results
Of the lncRNAs identified, LINC00639, RP4-676L2.1 and FENDRR were in ceRNA network established by our RNA-sequencing dataset. Using univariate Cox regression analysis, FENDRR was a risk factor of progression free survival (PFS) of stage I LUAD patients (HRs = 1.69, 95%CI 1.07–2.68, P < .050). Subsequently, diffe rential expression of FENDRR in paired normal and LUAD tissues was detected significant by real-time quantitative (qRT-PCR) (P < 0.001).
Conclusions
This study, for the first time, deciphered the regulatory role of FENDRR/miR-6815-5p axis in the progression of early-stage LUAD, which is needed to be established in vitro and in vivo.
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Yang Q, Chen Y, Guo R, Dai Y, Tang L, Zhao Y, Wu X, Li M, Du F, Shen J, Yi T, Xiao Z, Wen Q. Interaction of ncRNA and Epigenetic Modifications in Gastric Cancer: Focus on Histone Modification. Front Oncol 2022; 11:822745. [PMID: 35155211 PMCID: PMC8826423 DOI: 10.3389/fonc.2021.822745] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Accepted: 12/28/2021] [Indexed: 12/24/2022] Open
Abstract
Gastric cancer has developed as a very common gastrointestinal tumors, with recent effective advancements in the diagnosis and treatment of early gastric cancer. However, the prognosis for gastric cancer remains poor. As a result, there is in sore need of better understanding the mechanisms of gastric cancer development and progression to improve existing diagnostic and treatment options. In recent years, epigenetics has been recognized as an important contributor on tumor progression. Epigenetic changes in cancer include chromatin remodeling, DNA methylation and histone modifications. An increasing number of studies demonstrated that noncoding RNAs (ncRNAs) are associated with epigenetic changes in gastric cancer. Herein, we describe the molecular interactions of histone modifications and ncRNAs in epigenetics. We focus on ncRNA-mediated histone modifications of gene expression associated with tumorigenesis and progression in gastric cancer. This molecular mechanism will contribute to our deeper understanding of gastric carcinogenesis and progression, thus providing innovations in gastric cancer diagnosis and treatment strategies.
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Affiliation(s)
- Qingfan Yang
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, China.,South Sichuan Institute of Translational Medicine, Luzhou, China
| | - Yu Chen
- South Sichuan Institute of Translational Medicine, Luzhou, China.,Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China.,Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, China
| | - Rui Guo
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, China
| | - Yalan Dai
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, China.,South Sichuan Institute of Translational Medicine, Luzhou, China
| | - Liyao Tang
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China.,Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, China
| | - Yueshui Zhao
- South Sichuan Institute of Translational Medicine, Luzhou, China.,Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China.,Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, China
| | - Xu Wu
- South Sichuan Institute of Translational Medicine, Luzhou, China.,Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China.,Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, China
| | - Mingxing Li
- South Sichuan Institute of Translational Medicine, Luzhou, China.,Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China.,Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, China
| | - Fukuan Du
- South Sichuan Institute of Translational Medicine, Luzhou, China.,Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China.,Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, China
| | - Jing Shen
- South Sichuan Institute of Translational Medicine, Luzhou, China.,Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China.,Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, China
| | - Tao Yi
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, Hong Kong SAR, China
| | - Zhangang Xiao
- South Sichuan Institute of Translational Medicine, Luzhou, China.,Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China.,Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, China
| | - Qinglian Wen
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, China.,South Sichuan Institute of Translational Medicine, Luzhou, China
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25
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Ma J, Zhao G, Du J, Li J, Lin G, Zhang J. LncRNA FENDRR Inhibits Gastric Cancer Cell Proliferation and Invasion via the miR-421/SIRT3/Notch-1 Axis. Cancer Manag Res 2021; 13:9175-9187. [PMID: 34938121 PMCID: PMC8685553 DOI: 10.2147/cmar.s329419] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Accepted: 11/09/2021] [Indexed: 12/27/2022] Open
Abstract
Objective This study aimed to investigate the regulatory effect of lncRNA fetal-lethal non-coding developmental regulatory RNA (FENDRR) on gastric cancer (GC) progression. Methods The expression levels of FENDRR in GC tissues and paracancerous tissues, as well as in gastric normal epithelial cell line and GC cell lines were detected. The Ad-FENDRR or si-FENDRR was transfected into AGS and SGC-7901 cells, and cell proliferation, invasion and apoptosis were determined. Online bioinformatics database predicted and screened miR-421 as a potential target of FENDRR, and SIRT3 was predicted as a target gene of miR-421. The pcDNA-SIRT3 or si-SIRT3 was transfected into AGS cells, and cell proliferation, invasion, apoptosis and Notch-1 protein expression were determined. Ad-FENDRR was transfected into AGS and SGC-7901 cells alone or together with miR-421 mimic to explore the effect of miR-421 on cells. The AGS cells transfected with Ad-FENDRR were injected into the armpits of nude mice to establish subcutaneous xenograft tumor model, and tumor growth was observed. Results FENDRR expression was downregulated in GC tissues and cell lines. Overexpression of FENDRR or SIRT3 inhibited tumor proliferation and invasion, and promoted apoptosis. The overexpression of Notch-1 reversed the inhibitory effect of SIRT3 on AGS cell. MiR-421 mimic reversed the inhibitory effect of FENDRR on the growth of AGS and SGC-7901 cells. Nude mice injected with FENDRR overexpressing AGS cells had smaller tumor volume and weight and weaker tumor cell proliferation ability. Conclusion FENDRR inhibits Notch-1 pathway to inhibit GC cell proliferation and invasion by upregulating SIRT3 expression via targeting miR-421.
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Affiliation(s)
- Jia Ma
- Department of Surgical Oncology, Shaanxi Provincial People's Hospital, Xi'an, 710068, Shaanxi, People's Republic of China
| | - Gang Zhao
- Department of Surgical Oncology, Pucheng County Hospital, Weinan, 715500, Shaanxi, People's Republic of China
| | - Jia Du
- Department of Surgical Oncology, Shaanxi Provincial People's Hospital, Xi'an, 710068, Shaanxi, People's Republic of China
| | - Jiang Li
- Department of Surgical Oncology, Shaanxi Provincial People's Hospital, Xi'an, 710068, Shaanxi, People's Republic of China
| | - Guangshuai Lin
- Department of Surgical Oncology, Shaanxi Provincial People's Hospital, Xi'an, 710068, Shaanxi, People's Republic of China
| | - Jianfei Zhang
- Department of Surgical Oncology, Shaanxi Provincial People's Hospital, Xi'an, 710068, Shaanxi, People's Republic of China
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26
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Zhao Q, Pang G, Yang L, Chen S, Xu R, Shao W. Long Noncoding RNAs Regulate the Inflammatory Responses of Macrophages. Cells 2021; 11:cells11010005. [PMID: 35011565 PMCID: PMC8750547 DOI: 10.3390/cells11010005] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 12/12/2021] [Accepted: 12/15/2021] [Indexed: 12/18/2022] Open
Abstract
Long noncoding RNAs (lncRNAs) are defined as transcripts with more than 200 nucleotides that have little or no coding potential. In recent years, due to the development of next-generation sequencing (NGS), a large number of studies have revealed that lncRNAs function as key regulators to maintain immune balance and participate in diverse physiological and pathological processes in the human body. Notably, overwhelming evidence suggests that lncRNAs can regulate innate immune responses, the differentiation and development of immune cells, inflammatory autoimmune diseases, and many other immunological processes with distinct regulatory mechanisms. In this review, we summarized the emerging roles of lncRNAs in macrophage development and polarization. In addition, the potential value of lncRNAs as diagnostic biomarkers and novel therapeutic targets for the treatment of aberrant immune responses and inflammatory diseases are discussed.
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27
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Wei S, Dai S, Zhang C, Zhao R, Zhao Z, Song Y, Shan B, Zhao L. LncRNA NR038975, A Serum-Based Biomarker, Promotes Gastric Tumorigenesis by Interacting With NF90/NF45 Complex. Front Oncol 2021; 11:721604. [PMID: 34900675 PMCID: PMC8660099 DOI: 10.3389/fonc.2021.721604] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Accepted: 10/20/2021] [Indexed: 12/24/2022] Open
Abstract
Gastric cancer (GC) is one of the deadliest cancers, and long noncoding RNAs (lncRNAs) have been reported to be the important regulators during the occurrence and development of GC. The present study identified a novel and functional lncRNA in GC, named NR038975, which was confirmed to be markedly upregulated in the Gene Expression Profiling Interactive Analysis (GEPIA) dataset and our independent cohort of GC tissues. We firstly characterized the full-length sequence and subcellular location of NR038975 in GC cells. Our data demonstrated that upregulated NR038975 expression was significantly related to lymph node metastasis and TNM stage. In addition, knockdown of NR038975 inhibited GC cell proliferation, migration, invasion, and clonogenicity and vice versa. Mechanistically, RNA pull-down and mass spectrometry assays identified the NR038975-binding proteins and NF90/NF45 complex, and the binding was also confirmed by RNA immunoprecipitation and confocal experiments. We further demonstrated that genetic deficiency of NR038975 abrogated the interaction between NF45 and NF90. Moreover, NF90 increased the stability of NR038975. Thus, NR038975-NF90/NF45 will be an important combinational target of GC. Finally, we detected NR038975 in serum exosomes and serum of GC patients. Our results indicated that NR038975 was a biomarker for gastric tumorigenesis. The current study demonstrated that NR038975 is a novel lncRNA that is clinically and functionally engaged in GC progression and might be a novel diagnostic marker and potential therapeutic target.
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Affiliation(s)
- Sisi Wei
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Suli Dai
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Cong Zhang
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Ruinian Zhao
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Zitong Zhao
- State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yongmei Song
- State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Baoen Shan
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Lianmei Zhao
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
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28
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Zhang Y, Zhang PS, Rong ZY, Huang C. One stomach, two subtypes of carcinoma-the differences between distal and proximal gastric cancer. Gastroenterol Rep (Oxf) 2021; 9:489-504. [PMID: 34925847 PMCID: PMC8677565 DOI: 10.1093/gastro/goab050] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 07/13/2021] [Accepted: 08/13/2021] [Indexed: 12/13/2022] Open
Abstract
Gastric cancer (GC) is one of the most common malignant tumors of the digestive tract, posing a significant risk to human health. Over the past 10 years, the pathological characteristics and the prognosis of GC have been determined based on the locations of the tumors that were then classified into two types-proximal and distal GC. This review focuses on the differences in epidemiology, etiology, cell source, pathological characteristics, gene expression, molecular markers, manifestations, treatment, prognosis, and prevention between proximal and distal GC to provide guidance and a basis for clinical diagnosis and treatment.
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Affiliation(s)
- Yuan Zhang
- Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, P. R. China
| | - Peng-Shan Zhang
- Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, P. R. China
| | - Ze-Yin Rong
- Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, P. R. China
| | - Chen Huang
- Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, P. R. China
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Shi X, Liu X, Pan S, Ke Y, Li Y, Guo W, Wang Y, Ruan Q, Zhang X, Ma H. A Novel Autophagy-Related Long Non-Coding RNA Signature to Predict Prognosis and Therapeutic Response in Esophageal Squamous Cell Carcinoma. Int J Gen Med 2021; 14:8325-8339. [PMID: 34815705 PMCID: PMC8605829 DOI: 10.2147/ijgm.s333697] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 10/06/2021] [Indexed: 12/19/2022] Open
Abstract
Background Considering the significance of autophagy and long non-coding RNAs (lncRNAs) in the biology of esophageal squamous cell carcinoma (ESCC), the present study aimed to identify a new autophagy-related lncRNA signature to forecast the clinical outcomes of ESCC patients and to guide individualized treatment. Methods The expression profiles were obtained from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database. We extracted autophagy-related genes from the Human Autophagy Database and identified autophagy-related lncRNAs through Spearman correlation analysis. Univariate, least absolute shrinkage and selection operator and multivariate Cox regression analyses were performed on GSE53625 to construct an autophagy-related lncRNAs prognostic signature. The model was subjected to bootstrap internal validation, and the expression levels of lncRNAs were verified by TCGA database. The potential molecular mechanism of the model was explored by gene set enrichment analysis (GSEA). Spearman correlation coefficient examined the correlation between risk score and ferroptosis-associated genes as well as the response to immunotherapy and chemotherapy. Results We identified and validated an autophagy-related lncRNAs prognostic signature in 179 patients with ESCC. The prognosis of patients in the low-risk group was significantly better than that in the high-risk group (p-value <0.001). The reliability of the model was verified by Brier score and ROC. GSEA results showed significant enrichment of cancer- and autophagy-related signaling pathways in the high-risk group and metabolism-related pathways in the low-risk group. Correlation analysis indicated that the model can effectively forecast the effect of immunotherapy and chemotherapy. About 35.41% (74/209) ferroptosis-related genes were significantly correlated with risk scores. Conclusion In brief, we constructed a novel autophagy-related lncRNAs signature (LINC02024, LINC01711, LINC01419, LCAL1, FENDRR, ADAMTS9-AS1, AC025244.1, AC015908.6 and AC011997.1), which could improve the prediction of clinical outcomes and guide individualized treatment of ESCC patients.
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Affiliation(s)
- Xiaobo Shi
- Department of Radiation Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Xiaoxiao Liu
- Department of Radiation Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Shupei Pan
- Department of Radiation Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Yue Ke
- Department of Radiation Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Yuxing Li
- Department of Radiation Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Wei Guo
- Department of Radiation Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Yuchen Wang
- Department of Radiation Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Qinli Ruan
- Department of Radiation Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Xiaozhi Zhang
- Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Hongbing Ma
- Department of Radiation Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
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Ghalib Ibrahim Alnajar S, Rajabi A, Maydanchi M, Tayefeh Gholami S, Saber A, Safaralizadeh R. Overexpression of lncRNA AFAP1-AS1 as a diagnostic biomarker in non-small cell lung cancer. EGYPTIAN JOURNAL OF MEDICAL HUMAN GENETICS 2021. [DOI: 10.1186/s43042-021-00194-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Long non-coding RNAs (lncRNAs) play important roles in lung tumorigenesis. Among different lncRNAs, overexpression of the lncRNA actin filament‐associated protein 1‐antisense RNA 1 (AFAP1-AS1) in lung tumors has been reported in different studies. In the current study, we aimed to investigate the potential value of lncRNA AFAP1-AS1 as a diagnostic biomarker in lung cancer. Ninety samples from patients with lung cancer were collected from Noor-E-Nejat hospital, Tabriz, Iran. The expression of AFAP1-AS1 was assessed using quantitative reverse transcriptase-PCR (qRT-PCR), followed by the ROC curve analysis to investigate the biomarker potency of AFAP1-AS1.
Results
Our results revealed an upregulation of AFAP1-AS1 in tumor samples as compared to the adjacent non-tumor tissues. We found a significant positive association between AFAP1-AS1 expression and tumor size, as well as tumor stage.
Conclusions
Our results showed overexpression of AFAP1-AS1 and its capacity as a diagnostic biomarker in lung cancer.
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Yang F, Sun S, Yang F. Prognostic and Predicted Significance of FENDRR in Colon and Rectum Adenocarcinoma. Front Oncol 2021; 11:668595. [PMID: 34621665 PMCID: PMC8490734 DOI: 10.3389/fonc.2021.668595] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 09/06/2021] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND The role of fetal-lethal non-coding developmental regulatory RNA (FENDRR) has been explored in various cancers; however, its relationship with colon adenocarcinoma/rectum adenocarcinoma (COAD/READ) remains unclear. The objectives of this study were to identify and assess any associations between FENDRR and COAD/READ using The Cancer Genome Atlas (TCGA) database and the Genetic Data Commons (GDC) Data Portal. METHODS The records of patients with COAD/READ were collected from the GDC Data Portal. After comparing the expression level of FENDRR in COAD/READ and healthy tissues, we evaluated the association of FENDRR with clinicopathological characters and the survival rate, the impact of FENDRR on prognosis, the biological function of FENDRR, and the relative abundance of tumor-infiltrating immune cells in patients with COAD/READ. Moreover, we aimed to construct a protein-protein interaction (PPI) network for selecting genes and a ceRNA network for presenting mRNA-miRNA-lncRNA interactions. RESULTS In patients with COAD/READ, FENDRR expression could differentiate tumor tissues from the adjacent healthy tissues since it was significantly lower in the former than in the latter. High FENDRR expression was correlated with poorer survival and higher tumor stage, current tumor stage, and metastasis stage, and also exhibited high scores for apoptosis, autophagy, and senescence. Immune cell infiltration analysis showed that the high expression group had significantly lower immune and stromal scores. Low FENDRR expression was correlated with poor overall survival (OS), and thus, it could serve as an independent risk factor. The prognostic models constructed in the study performed well for the prediction of OS and disease-specific survival (DFS) using FENDRR expression. Gene set enrichment analysis revealed that vascular smooth muscle contraction, melanogenesis, basal cell carcinoma, and Hedgehog signaling pathways were significantly enriched in patients with high FENDRR expression. Eight hub genes, namely, PKM, ALDOA, PFKP, ALDOC, PYGL, CTNNB1, PSMA5, and WNT5A, were selected from the PPI network, and a ceRNA network was constructed based on the differentially expressed mRNAs, miRNAs, and lncRNAs to illustrate their regulatory relationships. CONCLUSION FENDRR may serve as a potential biomarker for the diagnosis and prognosis of COAD/READ.
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Affiliation(s)
| | - Siyu Sun
- Department of Gastroenterology, Sheng Jing Hospital of China Medical University, Shenyang, China
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Liu L, Dai A, Zhang Z, Ning M, Han D, Li L, Li Z. LncRNA PITPNA-AS1 promotes gastric cancer by increasing SOX4 expression via inhibition of miR-92a-3p. Aging (Albany NY) 2021; 13:21191-21201. [PMID: 34496348 PMCID: PMC8457584 DOI: 10.18632/aging.203403] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Accepted: 07/08/2021] [Indexed: 04/19/2023]
Abstract
BACKGROUND Gastric cancer (GC) is a malignant tumor of digestive tract with high mortality. Elucidating the molecular mechanisms of GC and obtaining new molecular targets are particularly important for the prevention and treatment of GC. The discovery of long non-coding RNAs (lncRNAs) provides the possibility for further elucidating the molecular mechanisms of GC and discovering new molecular markers. AIM Here, we aimed to explore the function and the mechanism of lncRNA PITPNA-AS1 in GC. METHODS High-throughput lncRNA microarray was used to compare the differences in expression profiles between tumor tissues and adjacent tissues, and to filtrate the differentially expressed lncRNAs in tumors. To analyze the relationship between lncRNA expression and clinicopathological parameters in GC. The apoptosis was detected by down-regulation of lncRNA. The effect of down-regulated lncRNA PITPNA-AS1 on the migration and invasion of GC cells was determined by wound healing and Transwell assays. The function of lncRNA PITPNA-AS1 on tumor growth was verified by tumor experiment in nude mice. Analysis of target interaction relationship was performed by luciferase assay. RESULTS The results of high throughput chip analysis identified that PITPNA-AS1 was up-regulated in GC tissues. Our data revealed that knockdown of PITPNA-AS1 was able to inhibit tumor development of GC cells. Meanwhile, PITPNA-AS1 could regulate SOX4 expression via targeting miR-92a-3p. CONCLUSION Thus, we concluded that PITPNA-AS1 induced the development of GC cells by inhibiting miR-92a-3p and inducing SOX4. Our finding presents novel insights of GC, which may provide an underlying therapeutic target for GC treatment.
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Affiliation(s)
- Licheng Liu
- Second Department of General Surgery, Cangzhou Central Hospital, Cangzhou, Hebei Province, China
| | - Anna Dai
- Meinian Health Clinic, Cangzhou, Hebei Province, China
| | - Zao Zhang
- Department of Pharmacy, Cangzhou City Center Hospital, Cangzhou, Hebei Province, China
| | - Meiying Ning
- Department of Pharmacy, Cangzhou City Center Hospital, Cangzhou, Hebei Province, China
| | - Dong Han
- Department of Pharmacy, Cangzhou City Center Hospital, Cangzhou, Hebei Province, China
| | - Li Li
- Department of Pharmacy, Cangzhou City Center Hospital, Cangzhou, Hebei Province, China
| | - Zhuangzhuang Li
- Department of Pharmacy, Cangzhou City Center Hospital, Cangzhou, Hebei Province, China
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Xu W, Wang B, Cai Y, Chen J, Meng E, Guo C, Zhou G, Yuan C. The Therapeutic Value and Molecular Mechanisms of lncRNA FENDRR in Human Cancer. Curr Pharm Des 2021; 27:4100-4106. [PMID: 34414867 DOI: 10.2174/1381612827666210820094702] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Accepted: 06/06/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND Long noncoding RNA (lncRNA) fetal-lethal non-coding developmental regulatory RNA (FENDRR), a newly known lncRNA, has been reported to be abnormally expressed in diverse tumors. This review is focused on clarifying the mechanism of FENDRR to regulate the biological process of tumors, affirming its value as a target for tumor therapy. METHODS The pathophysiological mechanism of FENDRR acting on tumors has been analyzed and summarized by reviewing PubMed. RESULTS The expression of lncRNA FENDRR is abnormally altered in clinical cancers, promoting the malignant transformation of a variety of tumors, including colon cancer, cervical cancer, hepatocellular carcinoma, prostate cancer, Malignant melanoma, lung cancer, osteosarcoma, breast cancer, etc. Cellular processions, including proliferation, invasion, apoptosis and migration affected by FENDRR, have been revealed. CONCLUSION Specific evidences for the involvement of LncRNA FENDRR in cancer regulatory processes suggest that FENDRR has the potential to be a biomarker or clinical therapeutic target for malignant tumors.
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Affiliation(s)
- Wen Xu
- College of Medical Science, China Three Gorges University, Yichang 443002, China
| | - Bei Wang
- College of Medical Science, China Three Gorges University, Yichang 443002, China
| | - Yuxuan Cai
- College of Medical Science, China Three Gorges University, Yichang 443002, China
| | - Jinlan Chen
- College of Medical Science, China Three Gorges University, Yichang 443002, China
| | - Enqing Meng
- College of Medical Science, China Three Gorges University, Yichang 443002, China
| | - Chong Guo
- College of Medical Science, China Three Gorges University, Yichang 443002, China
| | - Gang Zhou
- College of Traditional Chinese Medicine, China Three Gorges University, Yichang 443002, China
| | - Chengfu Yuan
- College of Medical Science, China Three Gorges University, Yichang 443002, China
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Liu Y, Wu Q, Fan X, Li W, Li X, Zhu H, Zhou Q, Yu J. A novel prognostic signature of immune-related lncRNA pairs in lung adenocarcinoma. Sci Rep 2021; 11:16794. [PMID: 34408216 PMCID: PMC8373953 DOI: 10.1038/s41598-021-96236-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Accepted: 08/06/2021] [Indexed: 02/05/2023] Open
Abstract
Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer, but the prognosis of LUAD patients remains unsatisfactory. Here, we retrieved the RNA-seq data of LUAD cohort from The Cancer Genome Atlas (TCGA) database and then identified differentially expressed immune-related lncRNAs (DEirlncRNAs) between LUAD and normal controls. Based on a new method of cyclically single pairing along with a 0-or-1 matrix, we constructed a novel prognostic signature of 8 DEirlncRNA pairs in LUAD with no dependence upon specific expression levels of lncRNAs. This prognostic model exhibited significant power in distinguishing good or poor prognosis of LUAD patients and the values of the area under the curve (AUC) were all over 0.70 in 1, 3, 5 years receiver operating characteristic (ROC) curves. Moreover, the risk score of the model could serve as an independent prognostic factor for patients with LUAD. In addition, the risk model was significantly associated with clinicopathological characteristics, tumor-infiltrating immune cells, immune-related molecules and sensitivity of anti-tumor drugs. This novel signature of DEirlncRNA pairs in LUAD, which did not require specific expression levels of lncRNAs, might be used to guide the administration of patients with LUAD in clinical practice.
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Affiliation(s)
- Yang Liu
- Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.,Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China
| | - Qiuhong Wu
- Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Xuejiao Fan
- Clinical Research Management Department, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Wen Li
- Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Xiaogang Li
- Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.,Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China
| | - Hui Zhu
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China
| | - Qinghua Zhou
- Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
| | - Jinming Yu
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China.
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Long Noncoding RNA FENDRR Inhibits Lung Fibroblast Proliferation via a Reduction of β-Catenin. Int J Mol Sci 2021; 22:ijms22168536. [PMID: 34445242 PMCID: PMC8395204 DOI: 10.3390/ijms22168536] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2021] [Revised: 07/30/2021] [Accepted: 08/01/2021] [Indexed: 02/06/2023] Open
Abstract
Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, and usually lethal lung disease and it has been widely accepted that fibroblast proliferation is one of the key characteristics of IPF. Long noncoding RNAs (lncRNAs) play vital roles in the pathogenesis of many diseases. In this study, we investigated the role of lncRNA FENDRR on fibroblast proliferation. Human lung fibroblasts stably overexpressing FENDRR showed a reduced cell proliferation compared to those expressing the control vector. On the other hand, FENDRR silencing increased fibroblast proliferation. FENDRR bound serine-arginine rich splicing factor 9 (SRSF9) and inhibited the phosphorylation of p70 ribosomal S6 kinase 1 (PS6K), a downstream protein of the mammalian target of rapamycin (mTOR) signaling. Silencing SRSF9 reduced fibroblast proliferation. FENDRR reduced β-catenin protein, but not mRNA levels. The reduction of β-catenin protein levels in lung fibroblasts by gene silencing or chemical inhibitor decreased fibroblast proliferation. Adenovirus-mediated FENDRR transfer to the lungs of mice reduced asbestos-induced fibrotic lesions and collagen deposition. RNA sequencing of lung tissues identified 7 cell proliferation-related genes that were up-regulated by asbestos but reversed by FENDRR. In conclusion, FENDRR inhibits fibroblast proliferation and functions as an anti-fibrotic lncRNA.
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Yousefi L, Osquee HO, Ghotaslou R, Rezaee MA, Pirzadeh T, Sadeghi J, Hemmati F, Yousefi B, Moaddab SY, Yousefi M, Shirmohammadi M, Somi MH, Ganbarov K, Kafil HS. Dysregulation of lncRNA in Helicobacter pylori-Infected Gastric Cancer Cells. BIOMED RESEARCH INTERNATIONAL 2021; 2021:6911734. [PMID: 34337048 PMCID: PMC8286195 DOI: 10.1155/2021/6911734] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 06/25/2021] [Accepted: 06/30/2021] [Indexed: 12/31/2022]
Abstract
Helicobacter pylori (H. pylori) infection is the most common cause of gastric cancer (GC). This microorganism is genetically diverse; GC is caused by several genetic deregulations in addition to environmental factors and bacterial virulence factors. lncRNAs (long noncoding RNAs) are significant biological macromolecules in GC, have specific functions in diseases, and could be therapeutic targets. Altered lncRNAs can lead to the abnormal expression of adjacent protein-coding genes, which may be important in cancer development. Their mechanisms have not been well understood, so we are going to investigate the risk of GC in a population with both high lncRNA and H. pylori infection.
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Affiliation(s)
- Leila Yousefi
- Student Research Committee, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hamid Owaysee Osquee
- Pharmaceutical Nanotechnology Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Reza Ghotaslou
- Pharmaceutical Nanotechnology Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Tahereh Pirzadeh
- Immunology Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Javid Sadeghi
- Immunology Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Fatemeh Hemmati
- Student Research Committee, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Bahman Yousefi
- Stem Cell Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Seyyed Yaghoub Moaddab
- Liver and Gastrointestinal Diseases Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mehdi Yousefi
- Stem Cell Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Masoud Shirmohammadi
- Liver and Gastrointestinal Diseases Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Hossein Somi
- Liver and Gastrointestinal Diseases Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Hossein Samadi Kafil
- Drug Applied Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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LncRNA FENDRR Expression Correlates with Tumor Immunogenicity. Genes (Basel) 2021; 12:genes12060897. [PMID: 34200642 PMCID: PMC8226633 DOI: 10.3390/genes12060897] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 06/03/2021] [Accepted: 06/08/2021] [Indexed: 01/06/2023] Open
Abstract
FENDRR (Fetal-lethal non-coding developmental regulatory RNA, LncRNA FOXF1-AS1) is a recently identified tumor suppressor long non-coding (LncRNA) RNA, and its expression has been linked with epigenetic modulation of the target genes involved in tumor immunity. In this study, we aimed to understand the role of FENDRR in predicting immune-responsiveness and the inflammatory tumor environment. Briefly, FENDRR expression and its relationship to immune activation signals were assessed in murine cell lines. Data suggested that tumor cells (e.g., C26 colon, 4T1 breast) that typically upregulate immune activation genes and the MHC class I molecule exhibited high FENDRR expression levels. Conversely, tumor cells with a generalized downregulation of immune-related gene expression (e.g., B16F10 melanoma) demonstrated low to undetectable FENDRR levels. Mechanistically, the modulation of FENDRR expression enhanced the inflammatory and WNT signaling pathways in tumors. Our early data suggest that FENDRR can play an important role in the development of immune-relevant phenotypes in tumors, and thereby improve cancer immunotherapy.
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Zhao SP, Yu C, Yang MS, Liu ZL, Yang BC, Xiao XF. Long Non-coding RNA FENDRR Modulates Autophagy Through Epigenetic Suppression of ATG7 via Binding PRC2 in Acute Pancreatitis. Inflammation 2021; 44:999-1013. [PMID: 33417179 DOI: 10.1007/s10753-020-01395-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 11/19/2020] [Accepted: 12/07/2020] [Indexed: 11/30/2022]
Abstract
Acute pancreatitis (AP) is an inflammatory, complicated pancreatic disease, carrying significant morbidity and mortality. However, the molecular and cellular mechanisms involved in AP pathogenesis remain to be elucidated. Here, we explore the role of FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR) in AP progression. Caerulein with or without LPS- induced or taurolithocholic acid 3-sulfate (TLC-S)-induced AP mouse models and cell models were performed for the validation of FENDRR expression in vivo and in vitro, respectively. Histopathological examinations of pancreatic tissues were performed to evaluate the severity of AP. Transmission electron microscopy was utilized to visualize the autophagic vacuoles. siRNA specifically targeting FENDRR was further applied. Flow cytometry was employed to assess cell apoptosis. ELISA, immunoflureoscence, and western blotting analysis were also performed to determine the levels of inflammatory cytokines and autophagy activity. RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays were carried out to reveal the epigenetic regulation of FENDRR on ATG7. Additionally, silencing FENDRR was also verified in AP mouse models. Higher FENDRR and impaired autophagy were displayed in both AP mouse models and cell models. FENDRR knockdown dramatically attenuated caerulein- or TLC-S-induced AR42J cells apoptosis and autophagy suppression. Further mechanistic experiments implied that the action of FENDRR is moderately attributable to its repression of ATG7 via direct interaction with the epigenetic repressor PRC2. Moreover, the silencing of FENDRR significantly induced the promotion of ATG7, thus alleviating the development of AP in vivo. Our study highlights FENDRR as a novel target that may contribute to AP progression, suggesting a therapeutic target for AP treatment.
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Affiliation(s)
- Shang-Ping Zhao
- The Third Xiangya Hospital of Central South University, No. 138, Tongzipo Road, Yuelu District, Changsha, 410013, Hunan Province, People's Republic of China
| | - Can Yu
- The Third Xiangya Hospital of Central South University, No. 138, Tongzipo Road, Yuelu District, Changsha, 410013, Hunan Province, People's Republic of China
| | - Ming-Shi Yang
- The Third Xiangya Hospital of Central South University, No. 138, Tongzipo Road, Yuelu District, Changsha, 410013, Hunan Province, People's Republic of China
| | - Zuo-Liang Liu
- The Third Xiangya Hospital of Central South University, No. 138, Tongzipo Road, Yuelu District, Changsha, 410013, Hunan Province, People's Republic of China
| | - Bing-Chang Yang
- The Third Xiangya Hospital of Central South University, No. 138, Tongzipo Road, Yuelu District, Changsha, 410013, Hunan Province, People's Republic of China
| | - Xue-Fei Xiao
- The Third Xiangya Hospital of Central South University, No. 138, Tongzipo Road, Yuelu District, Changsha, 410013, Hunan Province, People's Republic of China.
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Li X, Du Y, Wang Y. The value of LncRNA SNHG5 as a marker for the diagnosis and prognosis of gastric cancer. Am J Transl Res 2021; 13:5420-5427. [PMID: 34150139 PMCID: PMC8205807] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Accepted: 12/24/2020] [Indexed: 06/12/2023]
Abstract
OBJECTIVE To elucidate the value of serum lncRNA SNHG5 as a marker for the diagnosis and prognosis in gastric cancer. METHODS From January 2017 to January 2018, serum samples were collected from 50 cases of gastric cancer patients and 50 cases of benign gastrosia who underwent operations in our hospital, and 50 cases of healthy person. We detected the expression level of serum lncRNA SNHG5 in all research targets and the expression levels of LncRNA SNHG5 in the cancer adjacent tissues and cancer tissues of gastric cancer patients to analyze the relationship between serum LncRNA SNHG5 level and clinicopathological parameters. ROC curve was used to analyze its prognostic value of patients with gastric cancer, while Cox regression model was used to analyze the survival predictors of short-term adverse events. RESULTS The expression of lncRNA SNHG5 in the serum of gastric cancer was down-regulated, lower than that in the benign gastrosia group and healthy group (P < 0.05). The relative expression of lncRNA SNHG5 in cancer tissues was down-regulated compared with that in adjacent tissues (P < 0.05). lncRNA SNHG5 was correlated with drinking history and TNM stage (P < 0.05). The difference of serum lncRNA SNHG5 15 days and 1 month after operation was significant (P3 = 0.0001, P4 = 0.0135). The relative expression of serum lncRNA SNHG5 in the death group was noticeably lower than that in the survival group (P < 0.05). lncRNA SNHG5 is a survival predictor of short-term adverse events in patients with gastric cancer. CONCLUSION The expression of lncRNA SNHG5 in gastric cancer patients before operation and those with poor prognosis decreased. Therefore, it is of high diagnostic value in prognosis prediction and is expected to become a new molecular marker for early diagnosis of gastric cancer.
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Wang C, Meng X, Zhou Y, Yu J, Li Q, Liao Z, Gu Y, Han J, Linghu S, Jiao Z, Wang T, Zhang CY, Chen X. Long Noncoding RNA CTD-2245E15.3 Promotes Anabolic Enzymes ACC1 and PC to Support Non-Small Cell Lung Cancer Growth. Cancer Res 2021; 81:3509-3524. [PMID: 33941610 DOI: 10.1158/0008-5472.can-19-3806] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Revised: 09/09/2020] [Accepted: 04/29/2021] [Indexed: 11/16/2022]
Abstract
Long noncoding RNAs (lncRNA) have been shown to play critical regulatory roles in the onset and progression of human cancers. However, the functions of a large proportion of lncRNAs are still unexplored. Here we describe a novel lncRNA, CTD-2245E15.3, that promotes lung tumorigenesis by regulating the anabolic enzymes acetyl-CoA carboxylase 1 (ACC1, encoded by the ACACA gene) and pyruvate carboxylase (PC). Differentially expressed lncRNAs between non-small cell lung cancer (NSCLC) and paired adjacent nontumor tissues were identified by a microarray and validated using quantitative real-time polymerase chain reaction. CTD-2245E15.3 was significantly upregulated in NSCLC and was mainly located in the cytoplasm. Knockdown of CTD-2245E15.3 by specific antisense oligonucleotides suppressed cell growth in vitro and in vivo, largely due to cell-cycle arrest and induction of apoptosis. Overexpression of CTD-2245E15.3 in an orthotopic model of lung cancer led to a significant increase in total tumor burden. CTD-2245E15.3 exerted its oncogenic function by binding ACC1 and PC, which are key anabolic factors for biomolecule synthesis in rapidly proliferating tumor cells. Knockdown of CTD-2245E15.3 increased phosphorylation of ACC1 at an inhibitory site for enzymatic activity and promoted PC degradation via ubiquitination. Supplements of palmitate or oxaloacetate, products of ACC1 and PC, alleviated the suppression of cell growth caused by loss of CTD-2245E15.3. These findings reveal the important role of CTD-2245E15.3 as an oncogenic lncRNA in the anabolic process for tumor growth. SIGNIFICANCE: These findings demonstrate a novel lncRNA CTD-2245E15.3 that binds and positively regulates anabolic enzymes ACC1 and PC to promote tumor growth. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/13/3509/F1.large.jpg.
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Affiliation(s)
- Chen Wang
- State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
| | - Xiangfeng Meng
- State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China
| | - Yu Zhou
- State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China
| | - Jing Yu
- State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China
| | - Qing Li
- State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China
| | - Zhicong Liao
- Department of Cardiothoracic Surgery, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing Medical University, Nanjing, China
| | - Yuanyuan Gu
- State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China
| | - Jiayi Han
- Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Shuo Linghu
- State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China
| | - Zichen Jiao
- Department of Cardiothoracic Surgery, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing Medical University, Nanjing, China
| | - Tao Wang
- Department of Cardiothoracic Surgery, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing Medical University, Nanjing, China
| | - Chen-Yu Zhang
- State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
| | - Xi Chen
- State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
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Chen X, Wang D, Qian L. LncRNA Fetal-Lethal Noncoding Developmental Regulatory RNA (FENDRR) Suppresses Cell Proliferation and Promotes Apoptosis in Platelet Derived Growth Factor BB/Tumor Necrosis Factor α Induced Vascular Smooth Muscle Cells. J BIOMATER TISS ENG 2021. [DOI: 10.1166/jbt.2021.2660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Atherosclerosis is one of the primary causes that lead to cardiovascular disease. LncRNAs have been regarded as key modulators in many pathological processes. The study aims to identify the regulatory role of LncRNA fetal-lethal noncoding developmental regulatory RNA (FENDRR) in atherosclerosis.
Cell viability proliferation, cell cycle and cell apoptosis were evaluated by Cell Counting Kit-8 (CCK-8) assay flow cytometric analysis and western blot analysis. Quantitative real-time PCR (qRT-PCR) was carried out to determine FENDRR expression in PDGF-BB/TNF-α induced VSMCs.
Levels of TNF-α, IL-1, IL-6, MCP-1 and ICAM-1 were investigated by enzyme-linked immunosorbent assay (ELISA). The results showed that cell viability was enhanced and FENDRR expression was downregulated after VSMCs were induced by platelet derived growth factor BB (PDGF-BB) or
tumor necrosis factor a (TNF-α). Cell proliferation was inhibited by FENDRR overexpression in a time-dependent manner in PDGF-BB or TNF-α induced VSMCs. Moreover, FENDRR overexpression blocked cell cycle, suppressed the generations of TNF-α, IL-1, IL-6,
MCP-1 and ICAM-1, and facilitated cell apoptosis in VSMCs induced by PDGF-BB or TNF-α. These findings indicate the functional role of LncRNA FENDRR in atherosclerosis that attenuates cell proliferation and accelerates cell apoptosis.
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Affiliation(s)
- Xiaofang Chen
- Department of Cardiology The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
| | - Dongjin Wang
- Department of Cardiothoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
| | - Lingmei Qian
- Department of Cardiology The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
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Sun W, Ma G, Zhang L, Wang P, Zhang N, Wu Z, Dong Y, Cai F, Chen L, Liu H, Liang H, Deng J. DNMT3A-mediated silence in ADAMTS9 expression is restored by RNF180 to inhibit viability and motility in gastric cancer cells. Cell Death Dis 2021; 12:428. [PMID: 33931579 PMCID: PMC8087691 DOI: 10.1038/s41419-021-03628-5] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 03/16/2021] [Accepted: 03/16/2021] [Indexed: 12/24/2022]
Abstract
ADAMTS9 belongs to the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family, and its expression is frequently silenced due to promoter hypermethylation in various human cancers. However, the underlying mechanisms remain largely unknown. In this study, we investigated the inhibitory effects of ADAMTS9 on gastric cancer (GC) cells. We initially examined ADAMTS9 protein level in 135 GC and adjacent normal tissue pairs, showing that ADAMTS9 was strikingly decreased in the malignant specimens and patients with low ADAMTS9 expression exhibited more malignant phenotypes and poorer outcome. ADAMTS9 expression was restored in AGS and BGC-823 cells, which then markedly suppressed cellular viability and motility in vitro and in vivo. As ADAMTS9 was enriched in the nuclei of gastric mucosal cells, RNA-sequencing experiment showed that ADAMTS9 significantly altered gene expression profile in BGC-823 cells. Additionally, DNA methyltransferase 3α (DNMT3A) was identified to be responsible for the hypermethylation of ADAMTS9 promoter, and this methyltransferase was ubiquitinated by ring finger protein 180 (RNF180) and then subject to proteasome-mediated degradation. In conclusion, we uncovered RNF180/DNMT3A/ADAMTS9 axis in GC cells and showed how the signaling pathway affected GC cells.
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Affiliation(s)
- Weilin Sun
- Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Gang Ma
- Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Li Zhang
- Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Pengliang Wang
- Affiliated Cancer Hospital & institution of Guangzhou Medical University, Guangzhou, China
| | - Nannan Zhang
- Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Zizhen Wu
- Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Yinping Dong
- Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Fenglin Cai
- Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Liqiao Chen
- Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Huifang Liu
- Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Han Liang
- Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China.
| | - Jingyu Deng
- Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China.
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Wang XC, Liu Y, Long FW, Liu LR, Fan CW. Identification of a lncRNA prognostic signature-related to stem cell index and its significance in colorectal cancer. Future Oncol 2021; 17:3087-3100. [PMID: 33910362 DOI: 10.2217/fon-2020-1163] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Background: The relationship between long noncoding RNAs (lncRNAs) and the mRNA stemness index (mRNAsi) in colorectal cancer (CRC) is still unclear. Materials & methods: The mRNAsi, mRNAsi-related lncRNAs and their clinical significance were analyzed by bioinformatic approaches in The Cancer Genome Atlas (TCGA)-COREAD dataset. Results: mRNAsi was negatively related to pathological features but positively related to overall survival and recurrence-free survival in CRC. A five mRNAsi-related lncRNAs prognostic signature was further developed and showed independent prognostic factors related to overall survival in CRC patients, due to the five mRNAsi-related lncRNAs involved in several pathways of the cancer stem cells and malignant cancer cell phenotypes. Conclusion: The present study highlights the potential roles of mRNAsi-related lncRNAs as alternative prognostic markers.
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Affiliation(s)
- Xiao-Cheng Wang
- Department of Day Surgery Center, West China Hospital, Sichuan University, Chengdu, 610041, China.,Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Ya Liu
- Department of Internal Medicine, Chengdu City Jinniu District No. 2 People's Hospital, Chengdu, 610036, China
| | - Fei-Wu Long
- Department of Gastrointestinal Surgery & Breast & Thyroid Surgery, Minimally Invasive Surgery, West China School of Public Health & West China Fourth Hospital, Sichuan University, Chengdu, 610041, China
| | - Liang-Ren Liu
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Chuan-Wen Fan
- Department of Gastrointestinal Surgery & Breast & Thyroid Surgery, Minimally Invasive Surgery, West China School of Public Health & West China Fourth Hospital, Sichuan University, Chengdu, 610041, China.,Department of Oncology & Department of Biomedical & Clinical Sciences, Linköping University, Linköping, 58183, Sweden
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Wang LQ, Zheng YY, Zhou HJ, Zhang XX, Wu P, Zhu SM. LncRNA-Fendrr protects against the ubiquitination and degradation of NLRC4 protein through HERC2 to regulate the pyroptosis of microglia. Mol Med 2021; 27:39. [PMID: 33858325 PMCID: PMC8048261 DOI: 10.1186/s10020-021-00299-y] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Accepted: 04/05/2021] [Indexed: 12/11/2022] Open
Abstract
OBJECTIVES Targeted inhibition of inflammatory response can reduce diabetic cerebral ischemia-reperfusion (I/R) injure. Pyroptosis is characterized by caspase-1 dependence and the release of a large number of pro-inflammatory factors. LncRNA-Fendrr is associated with a variety of diseases, but Fendrr has not been studied in diabetic cerebral I/R. NLR-family CARD-containing protein 4 (NLRC4) regulate the pyroptosis of microglia cells. This study was designed to investigate whether Fendrr is involved in the effects of diabetic cerebral I/R injury. METHODS The diabetic brain I/R model in mice was constructed. Mouse microglia cell line BV-2 cells were exposed to high glucose followed by hypoxia/reoxygenation (H/R). Fendrr and some pyroptosis-associated proteins were detected by qRT-PCR, western blot or ELISA. HE staining was used to detect pathological changes. Microglia pyroptosis was detected by TUNEL staining. RNA pull-down and RNA Immunoprecipitation were used to detect binding of Fendrr to HERC2 (E3 ubiquitin ligase), and CO-IP detected binding of HERC2 to NLRC4. The ubiquitination of NLRC4 was detected by ubiquitination experiments. RESULTS Fendrr was significantly increased in the diabetic cerebral I/R model, and NLRC4 inflammatory complex and pyroptosis mediated inflammatory factors were increased. NLRC4 and inflammatory cytokines associated with pyroptosis were decreased in the high glucose-treated hypoxia/reoxygenation (H/R)-induced microglia after Fendrr knockdown. Fendrr bound to HERC2 protein, and HERC2 bound to NLRC4. Meanwhile, Fendrr could inhibit the ubiquitination of NLRC4, HERC2 promoted the ubiquitination of NLRC4 protein. Moreover, the effect of Fendrr overexpression in the diabetic cerebral I/R model of microglia can be reversed by HERC2 overexpression. CONCLUSION Fendrr can protect against the ubiquitination and degradation of NLRC4 protein through E3 ubiquitin ligase HERC2, thereby accelerating the pyroptosis of microglia.
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Affiliation(s)
- Li-Qing Wang
- Department of Anesthesiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, People's Republic of China
| | - Yue-Ying Zheng
- Department of Anesthesiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, People's Republic of China
| | - Heng-Jun Zhou
- Department of Neurosurgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, People's Republic of China
| | - Xiong-Xin Zhang
- Department of Anesthesiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, People's Republic of China
| | - Pin Wu
- Department of Anesthesiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, People's Republic of China
| | - Sheng-Mei Zhu
- Department of Anesthesiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, People's Republic of China.
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Szafranski P, Gambin T, Karolak JA, Popek E, Stankiewicz P. Lung-specific distant enhancer cis regulates expression of FOXF1 and lncRNA FENDRR. Hum Mutat 2021; 42:694-698. [PMID: 33739555 DOI: 10.1002/humu.24198] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Revised: 02/22/2021] [Accepted: 03/14/2021] [Indexed: 12/21/2022]
Abstract
The FOXF1 gene, causative for a neonatal lethal lung developmental disorder alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV), maps 1.7 kb away from the long noncoding RNA gene FENDRR on the opposite strand, suggesting they may be coregulated. Using RNA sequencing in lung tissue from ACDMPV patients with heterozygous deletions of the FOXF1 distant enhancer located 286 kb upstream, leaving FOXF1 and FENDRR intact, we have found that the FENDRR and FOXF1 expressions were reduced by approximately 75% and 50%, respectively, and were monoallelic from the intact chromosome 16q24.1. In contrast, ACDMPV patients with FOXF1 SNVs had biallelic FENDRR expression reduced by 66%-82%. Corroboratively, depletion of FOXF1 by small interfering RNA in lung fibroblasts resulted in a 50% decrease of FENDRR expression. These data indicate that FENDRR expression in the lungs is regulated both in cis by the FOXF1 distant enhancer and in trans by FOXF1. Our findings are compatible with the involvement of FENDRR in FOXF1-related disorders, including ACDMPV.
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Affiliation(s)
- Przemyslaw Szafranski
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
| | - Tomasz Gambin
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.,Institute of Computer Science, Warsaw University of Technology, Warsaw, Poland.,Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland
| | - Justyna A Karolak
- Chair and Department of Genetics and Pharmaceutical Microbiology, Poznań University of Medical Sciences, Poznań, Poland
| | - Edwina Popek
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA
| | - Paweł Stankiewicz
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
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Zhao Q, Xie J, Xie J, Zhao R, Song C, Wang H, Rong J, Yan L, Song Y, Wang F, Xie Y. Weighted correlation network analysis identifies FN1, COL1A1 and SERPINE1 associated with the progression and prognosis of gastric cancer. Cancer Biomark 2021; 31:59-75. [PMID: 33780362 DOI: 10.3233/cbm-200594] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND Gastric cancer (GC) is one of the most deadliest tumours worldwide, and its prognosis remains poor. OBJECTIVE This study aims to identify and validate hub genes associated with the progression and prognosis of GC by constructing a weighted correlation network. METHODS The gene co-expression network was constructed by the WGCNA package based on GC samples and clinical data from the TCGA database. The module of interest that was highly related to clinical traits, including stage, grade and overall survival (OS), was identified. GO and KEGG pathway enrichment analyses were performed using the clusterprofiler package in R. Cytoscape software was used to identify the 10 hub genes. Differential expression and survival analyses were performed on GEPIA web resources and verified by four GEO datasets and our clinical gastric specimens. The receiver operating characteristic (ROC) curves of hub genes were plotted using the pROC package in R. The potential pathogenic mechanisms of hub genes were analysed using gene set enrichment analysis (GSEA) software. RESULTS A total of ten modules were detected, and the magenta module was identified as highly related to OS, stage and grade. Enrichment analysis of magenta module indicated that ECM-receptor interaction, focal adhesion, PI3K-Akt pathway, proteoglycans in cancer were significantly enriched. The PPI network identified ten hub genes, namely COL1A1, COL1A2, FN1, POSTN, THBS2, COL11A1, SPP1, MMP13, COMP, and SERPINE1. Three hub genes (FN1, COL1A1 and SERPINE1) were finally identified to be associated with carcinogenicity and poor prognosis of GC, and all were independent risk factors for GC. The area under the curve (AUC) values of FN1, COL1A1 and SERPINE1 for the prediction of GC were 0.702, 0.917 and 0.812, respectively. GSEA showed that three hub genes share 15 common upregulated biological pathways, including hypoxia, epithelial mesenchymal transition, angiogenesis, and apoptosis. CONCLUSION We identified FN1, COL1A1 and SERPINE1 as being associated with the progression and poor prognosis of GC.
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Affiliation(s)
- Qiaoyun Zhao
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Donghu District, Nanchang, Jiangxi, China.,Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Donghu District, Nanchang, Jiangxi, China
| | - Jun Xie
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Donghu District, Nanchang, Jiangxi, China.,Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Donghu District, Nanchang, Jiangxi, China
| | - Jinliang Xie
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Donghu District, Nanchang, Jiangxi, China
| | - Rulin Zhao
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Donghu District, Nanchang, Jiangxi, China
| | - Conghua Song
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Donghu District, Nanchang, Jiangxi, China
| | - Huan Wang
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Donghu District, Nanchang, Jiangxi, China
| | - Jianfang Rong
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Donghu District, Nanchang, Jiangxi, China
| | - Lili Yan
- Laboratory of Biochemistry and Molecular Biology, Jiangxi Institute of Medical Sciences, Donghu District, Nanchang, Jiangxi, China
| | - Yanping Song
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Donghu District, Nanchang, Jiangxi, China
| | - Fangfei Wang
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Donghu District, Nanchang, Jiangxi, China
| | - Yong Xie
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Donghu District, Nanchang, Jiangxi, China
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Liu H, Zhang Z, Han Y, Fan A, Liu H, Zhang X, Liu Y, Zhang R, Liu W, Lu Y, Fan D, Zhao X, Nie Y. The FENDRR/FOXC2 Axis Contributes to Multidrug Resistance in Gastric Cancer and Correlates With Poor Prognosis. Front Oncol 2021; 11:634579. [PMID: 33869020 PMCID: PMC8044876 DOI: 10.3389/fonc.2021.634579] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2020] [Accepted: 01/22/2021] [Indexed: 12/23/2022] Open
Abstract
The dysregulation of long non-coding RNAs (lncRNAs) and transcription factors (TFs) is closely related to the development and progression of drug resistance in cancer chemotherapy. However, their regulatory interactions in the multidrug resistance (MDR) of gastric cancer (GC) has largely remained unknown. In this study, we report a novel oncogenic role of lncRNA FENDRR in conferring MDR in GC by coordinated regulation of FOXC2 expression at the transcriptional and posttranscriptional levels. In vitro and in vivo experiments demonstrated that downregulation of FENDRR expression remarkably decreased drug resistant ability of GC MDR cells while upregulation of FENDRR expression produced the opposite effect. FENDRR overexpression was observed in MDR GC cell lines, patient-derived xenografts, and clinical samples. And the high levels of FENDRR expression were correlated with poor prognosis in GC patients. Regarding the mechanism, FENDRR was revealed to increase proto-oncogene FOXC2 transcription by performing an enhancer-like role in the nucleus and by sponging miR-4700-3p in the cytoplasm. Both FOXC2 and miR-4700-3p were shown to be functionally involved in the FENDRR-induced chemoresistance. In addition, there is a positive correlation between FENDRR and FOXC2 expression in clinic and the overexpressed FOXC2 indicated a poor prognosis in GC patients. Collectively, our findings provide a new perspective for the lncRNA-TF regulatory interaction involved in MDR, suggesting that targeting the FENDRR/FOXC2 axis may be an effective approach to circumvent GC chemoresistance.
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Affiliation(s)
- Hao Liu
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Zhe Zhang
- Department of Gastroenterology and Hepatology, Hainan Branch of Chinese PLA General Hospital, Sanya, China
| | - Yanan Han
- Department of Gastroenterology, Xi'an Children's Hospital, Xi'an, China
| | - Ahui Fan
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Haiming Liu
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.,School of Software Engineering, Beijing Jiaotong University, Beijing, China
| | - Xiangyuan Zhang
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.,Department of Gastroenterology and Hepatology, 952 Hospital of the Chinese PLA Ground Force, Golmud, China
| | - Yanhong Liu
- Department of Traditional Chinese Medicine Physical Therapy and Rehabilitation, Seventy-Fourth Army of the PLA Hospital, Guangzhou, China
| | - Rugang Zhang
- Department of Gastroenterology and Hepatology, Hainan Branch of Chinese PLA General Hospital, Sanya, China
| | - Wanning Liu
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.,College of Life Sciences, Northwest University, Xi'an, China
| | - Yuanyuan Lu
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Daiming Fan
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Xiaodi Zhao
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Yongzhan Nie
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
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Zhang J, Xu X, Yin J, Tang J, Hu N, Hong Y, Song Z, Bian B, Wu F. lncRNA OGFRP1 promotes tumor progression by activating the AKT/mTOR pathway in human gastric cancer. Aging (Albany NY) 2021; 13:9766-9779. [PMID: 33744848 PMCID: PMC8064230 DOI: 10.18632/aging.202731] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Accepted: 10/20/2020] [Indexed: 12/14/2022]
Abstract
As biomolecules of great clinical value, lncRNAs play a crucial role as regulators in the processes of tumor origin, metastasis, and recurrence. Thus, lncRNAs are urgently needed for research in gastric cancer. We elucidated the specific function of OGFRP1, both in vitro and in vivo. OGFRP1 was expressed at abnormally high levels in gastric cancer samples (n = 408) compared to normal samples (n = 211). Similar results were obtained in 30 clinical case samples. Interference of OGFRP1 markedly blocked cell proliferation and migration, and it induced cell cycle arrest and the apoptosis of gastric cancer cells in vitro. Phosphorylation of AKT was inhibited in cells transfected with OGFRP1 siRNA, as compared to their control cells. The in vivo results further confirmed the antitumor effects of OGFRP1 knockdown on gastric cancer. Decreases in tumor volume (104.23±62.27 mm3) and weight (0.1006±0.0488 g) in nude mice were observed during the OGFRP1 interference, as compared with the control group (418.96±211.96 mm3 and 0.2741±0.0769 g). OGFRP1 promotes tumor progression through activating the AKT/mTOR pathway. Our findings provide a new potential target for the clinical treatment of human gastric cancer.
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Affiliation(s)
- Jingzhou Zhang
- Department of Oncology, Lianyungang Clinical College of Nanjing Medical University, The First People's Hospital of Lianyungang, Lianyungang, China
| | - Xiujuan Xu
- Department of Radiation Oncology, Lianyungang Second People's Hospital, Lianyungang, China
| | - Junfeng Yin
- Department of General Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Jiaqi Tang
- Department of Oncology, Lianyungang Clinical College of Nanjing Medical University, The First People's Hospital of Lianyungang, Lianyungang, China
| | - Nan Hu
- Department of Oncology, Lianyungang Clinical College of Nanjing Medical University, The First People's Hospital of Lianyungang, Lianyungang, China
| | - Yidong Hong
- Deparment of Oncology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Ziyan Song
- Department of Oncology, Lianyungang Clinical College of Nanjing Medical University, The First People's Hospital of Lianyungang, Lianyungang, China
| | - Baoxiang Bian
- Department of Oncology, Lianyungang Clinical College of Nanjing Medical University, The First People's Hospital of Lianyungang, Lianyungang, China
| | - Fenglei Wu
- Department of Oncology, Lianyungang Clinical College of Nanjing Medical University, The First People's Hospital of Lianyungang, Lianyungang, China
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Zong Z, Hu CG, Zhou TC, Yu ZM, Tang FX, Tian HK, Li H, Wang H. Nine-long non-coding ribonucleic acid signature can improve the survival prediction of colorectal cancer. World J Gastrointest Surg 2021; 13:210-221. [PMID: 33643540 PMCID: PMC7898191 DOI: 10.4240/wjgs.v13.i2.210] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2020] [Revised: 11/30/2020] [Accepted: 12/17/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Investigating molecular biomarkers that accurately predict prognosis is of considerable clinical significance. Accumulating evidence suggests that long non-coding ribonucleic acids (lncRNAs) are frequently aberrantly expressed in colorectal cancer (CRC).
AIM To elucidate the prognostic function of multiple lncRNAs serving as biomarkers in CRC.
METHODS We performed lncRNA expression profiling using the lncRNA mining approach in large CRC cohorts from The Cancer Genome Atlas (TCGA) database. Receiver operating characteristic analysis was performed to identify the optimal cutoff point at which patients could be classified into the high-risk or low-risk groups. Based on the Cox coefficient of the individual lncRNAs, we identified a nine-lncRNA signature that was associated with the survival of CRC patients in the training set (n = 175). The prognostic value of this nine-lncRNA signature was validated in the testing set (n = 174) and TCGA set (n = 349). The prognostic models, consisting of these nine CRC-specific lncRNAs, performed well for risk stratification in the testing set and TCGA set. Time-dependent receiver operating characteristic analysis indicated that this predictive model had good performance.
RESULTS Multivariate Cox regression and stratification analysis demonstrated that this nine-lncRNA signature was independent of other clinical features in predicting overall survival. Functional enrichment analysis of Kyoto Encyclopedia of Genes and Genomes pathways and Gene Ontology terms further indicated that these nine prognostic lncRNAs were closely associated with carcinogenesis-associated pathways and biological functions in CRC.
CONCLUSION A nine-lncRNA expression signature was identified and validated that could improve the prognosis prediction of CRC, thereby providing potential prognostic biomarkers and efficient therapeutic targets for patients with CRC.
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Affiliation(s)
- Zhen Zong
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Ce-Gui Hu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Tai-Cheng Zhou
- Department of Gastrointestinal Surgery and Hernia Center, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
| | - Zhuo-Min Yu
- Department of Gastrointestinal Surgery and Hernia Center, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
| | - Fu-Xin Tang
- Department of Gastrointestinal Surgery and Hernia Center, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
| | - Hua-Kai Tian
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Hui Li
- Department of Rheumatology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - He Wang
- Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
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50
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Zheng Q, Zhang Q, Yu X, He Y, Guo W. FENDRR: A pivotal, cancer-related, long non-coding RNA. Biomed Pharmacother 2021; 137:111390. [PMID: 33761608 DOI: 10.1016/j.biopha.2021.111390] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2021] [Revised: 02/08/2021] [Accepted: 02/09/2021] [Indexed: 12/27/2022] Open
Abstract
Long non-coding RNAs (lncRNAs) have more than 200 nucleotides and do not encode proteins. Based on numerous studies, lncRNAs have emerged as new and crucial regulators of biological function and have been implicated in the pathogenesis of a variety of diseases, especially cancers. Specific lncRNAs have been identified as novel molecular biomarkers for cancer diagnosis, prognosis, and treatment efficacy. Fetal-lethal non-coding developmental regulatory RNA (FENDRR, also known as FOXF1-AS1) is a novel lncRNA that is located at chr3q13.31 and has four exons and 3099 nucleotides, and its genomic site is located at chr3q13.31. FENDRR is abnormally expressed in a variety of cancers and is significantly associated with different clinical characteristics. In addition, FENDRR has shown potential as a biomarker for cancer diagnosis, prognosis, and treatment. In this review, we summarize the current understanding of FENDRR and its mechanistic role in cancer progression. We also discuss recent insights into the clinical significance of FENDRR for cancer diagnosis, prognosis, and treatment.
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Affiliation(s)
- Qingyuan Zheng
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou 450052, China; Henan Key Laboratory of Digestive Organ Transplantation, Zhengzhou 450052, China
| | - Qiyao Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou 450052, China; Henan Key Laboratory of Digestive Organ Transplantation, Zhengzhou 450052, China
| | - Xiao Yu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou 450052, China; Henan Key Laboratory of Digestive Organ Transplantation, Zhengzhou 450052, China
| | - Yuting He
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou 450052, China; Henan Key Laboratory of Digestive Organ Transplantation, Zhengzhou 450052, China.
| | - Wenzhi Guo
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou 450052, China; Henan Key Laboratory of Digestive Organ Transplantation, Zhengzhou 450052, China.
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