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1
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Liang W, Zhao Y, Meng Q, Jiang W, Deng S, Xue J. The role of long non-coding RNA in hepatocellular carcinoma. Aging (Albany NY) 2024; 16:4052-4073. [PMID: 38334963 PMCID: PMC10929815 DOI: 10.18632/aging.205523] [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: 05/19/2023] [Accepted: 12/12/2023] [Indexed: 02/10/2024]
Abstract
Hepatocellular carcinoma (HCC) is a prevalent liver malignancy with complex etiology and generally poor prognosis. Recently, long non-coding RNAs (lncRNAs), non-protein-coding RNA molecules exceeding 200 nucleotides, have emerged as pivotal players in HCC, influencing its initiation, progression, invasion, and metastasis. These lncRNAs modulate gene expression at epigenetic, transcriptional, and post-transcriptional levels, actively participating in the pathological and physiological processes of HCC. Understanding the intricate relationship between lncRNAs and HCC is important for improving prognosis and reducing mortality. This review summarizes advancements in elucidating the role of lncRNAs in HCC pathogenesis.
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Affiliation(s)
- Weizheng Liang
- Central Laboratory, The First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, Hebei, China
- Department of General Surgery, The First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, Hebei, China
- Tumor Research Institute, The First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, Hebei, China
| | - Yan Zhao
- Department of Mathematics and Computer Science, Free University Berlin, Berlin 14195, Germany
| | - Qingxue Meng
- Technology Department, The First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, Hebei, China
| | - Wenjie Jiang
- Department of Artificial Intelligence and Data Science, Hebei University of Technology, Tianjin 300401, China
| | - Shoulong Deng
- National Health Commission of China (NHC) Key Laboratory of Human Disease Comparative Medicine, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing 100021, China
| | - Jun Xue
- Department of General Surgery, The First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, Hebei, China
- Tumor Research Institute, The First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, Hebei, China
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Al-Noshokaty TM, Mansour A, Abdelhamid R, Abdellatif N, Alaaeldien A, Reda T, Abdelmaksoud NM, Doghish AS, Abulsoud AI, Elshaer SS. Role of long non-coding RNAs in pancreatic cancer pathogenesis and treatment resistance- A review. Pathol Res Pract 2023; 245:154438. [PMID: 37043965 DOI: 10.1016/j.prp.2023.154438] [Citation(s) in RCA: 38] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Revised: 03/30/2023] [Accepted: 04/02/2023] [Indexed: 04/14/2023]
Abstract
Pancreatic cancer (PC) is one of the deadliest cancers associated with poor prognosis. The lack of reliable means of early cancer detection contributes to this disease's dismal prognosis. Long non-coding RNAs (LncRNAs) are protein-free RNAs produced by genome transcription; they play critical roles in gene expression regulation, epigenetic modification, cell proliferation, differentiation, and reproduction. Recent research has shown that lncRNAs play important regulatory roles in PC behaviors, in addition to their recently found functions. Several in-depth investigations have shown that lncRNAs are strongly linked to PC development and progression. Here, we discuss how lncRNAs, which are often overlooked, play many roles as regulators in the molecular mechanism underlying PC. This review also discusses the involved LncRNAs in PC pathogenesis and treatment resistance.
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Affiliation(s)
- Tohada M Al-Noshokaty
- Department of Biochemistry, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Abdallah Mansour
- Department of Biochemistry, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Rehab Abdelhamid
- Department of Biochemistry, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Nourhan Abdellatif
- Department of Biochemistry, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Ayat Alaaeldien
- Department of Biochemistry, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Tasnim Reda
- Department of Biochemistry, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Nourhan M Abdelmaksoud
- Department of Biochemistry, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Ahmed S Doghish
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr, Cairo 11829, Egypt; Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr, Cairo 11231, Egypt.
| | - Ahmed I Abulsoud
- Department of Biochemistry, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt; Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr, Cairo 11231, Egypt.
| | - Shereen Saeid Elshaer
- Department of Biochemistry, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt; Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Girls), Al-Azhar University, Nasr, Cairo, Egypt
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3
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Anbiyaiee A, Ramazii M, Bajestani SS, Meybodi SM, Keivan M, Khoshnam SE, Farzaneh M. The function of LncRNA-ATB in cancer. CLINICAL & TRANSLATIONAL ONCOLOGY : OFFICIAL PUBLICATION OF THE FEDERATION OF SPANISH ONCOLOGY SOCIETIES AND OF THE NATIONAL CANCER INSTITUTE OF MEXICO 2023; 25:1-9. [PMID: 35597865 DOI: 10.1007/s12094-022-02848-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 04/25/2022] [Indexed: 01/07/2023]
Abstract
Cancer as a progressive and complex disease is caused by early chromosomal changes and stimulated cellular transformation. Previous studies reported that long non-coding RNAs (lncRNAs) play pivotal roles in the initiation, maintenance, and progression of cancer cells. LncRNA activated by TGF-β (ATB) has been shown to be dysregulated in different types of cancer. Aberrant expression of lncRNA-ATB plays an important role in the progression of diverse malignancies. High expression of LncRNA-ATB is associated with cancer cell growth, proliferation, metastasis, and EMT. LncRNA-ATB by targeting various signaling pathways and microRNAs (miRNAs) can trigger cancer pathogenesis. Therefore, lncRNA-ATB can be a novel target for cancer prediction and diagnosis. In this review, we will focus on the function of lncRNA-ATB in various types of human cancers.
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Affiliation(s)
- Amir Anbiyaiee
- Department of Surgery, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mohammad Ramazii
- Kerman University of Medical Sciences, University of Kerman, Kerman, Iran
| | | | | | - Mona Keivan
- Fertility and Infertility Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Seyed Esmaeil Khoshnam
- Persian Gulf Physiology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Maryam Farzaneh
- Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
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Xiaotan Sanjie Decoction Inhibits Gastric Cancer Cell Proliferation, Migration, and Invasion through lncRNA-ATB and miR-200A. BIOMED RESEARCH INTERNATIONAL 2022; 2022:7029182. [PMID: 36060143 PMCID: PMC9436559 DOI: 10.1155/2022/7029182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 07/08/2022] [Accepted: 07/11/2022] [Indexed: 11/24/2022]
Abstract
This study is aimed at exploring whether Xiaotan Sanjie decoction (XTSJ) inhibits gastric cancer (GC) proliferation and metastasis by regulating lncRNA-ATB expression. qRT-PCR and Western blot were used to analyze lncRNA-ATB and downstream-regulated genes/proteins in human GC cells. CCK8, Edu, and flow cytometry assays were used to detect the inhibitory effect of XTSJ on cell proliferation and apoptosis. Moreover, transwell and wound healing assays were used to detect the inhibitory effect of XTSJ on migration and invasion. qRT-PCR and Western blot were used to detect regulated genes and proteins levels. The HGC-27 cell line was used for follow-up analysis due to the high level of lncRNA-ATB and cell characteristics. XTSJ inhibited the proliferation and metastasis of HGC-27 in a dose-dependent manner. Further research found that XTSJ downregulated lncRNA-ATB, Vimentin, and N-cadherin, while it upregulated miR-200a and E-cadherin in a dose-dependent manner. XTSJ also upregulated Caspase 3, Caspase 9, Bax, and downregulated Bcl-2. Furthermore, XTSJ inhibited tumor growth in vivo and downregulated EMT signaling pathways. These results indicate that XTSJ may affect EMT and Bcl-2 signaling pathways by regulating lncRNA-ATB and miR-200a, thus inhibiting proliferation, migration, and invasion of HGC-27 cells. Therefore, XTSJ may be an effective treatment for the high levels of lncRNA-ATB in GC.
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Lu C, Wei D, Zhang Y, Wang P, Zhang W. Long Non-Coding RNAs as Potential Diagnostic and Prognostic Biomarkers in Breast Cancer: Progress and Prospects. Front Oncol 2021; 11:710538. [PMID: 34527584 PMCID: PMC8436618 DOI: 10.3389/fonc.2021.710538] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Accepted: 08/09/2021] [Indexed: 01/05/2023] Open
Abstract
Breast cancer is the most common malignancy among women worldwide, excluding non-melanoma skin cancer. It is now well understood that breast cancer is a heterogeneous entity that exhibits distinctive histological and biological features, treatment responses and prognostic patterns. Therefore, the identification of novel ideal diagnostic and prognostic biomarkers is of utmost importance. Long non-coding RNAs (lncRNAs) are commonly defined as transcripts longer than 200 nucleotides that lack coding potential. Extensive research has shown that lncRNAs are involved in multiple human cancers, including breast cancer. LncRNAs with dysregulated expression can act as oncogenes or tumor-suppressor genes to regulate malignant transformation processes, such as proliferation, invasion, migration and drug resistance. Intriguingly, the expression profiles of lncRNAs tend to be highly cell-type-specific, tissue-specific, disease-specific or developmental stage-specific, which makes them suitable biomarkers for breast cancer diagnosis and prognosis.
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Affiliation(s)
- Cuicui Lu
- Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Duncan Wei
- Department of Pharmacy, The First Affiliated Hospital of Medical College of Shantou University, Shantou, China
| | - Yahui Zhang
- Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Peng Wang
- Department of Pharmacy, The First Affiliated Hospital of Shandong First Medical University, Jinan, China
| | - Wen Zhang
- Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
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Long noncoding RNA LINC00261 upregulates ITIH5 to impair tumorigenic ability of pancreatic cancer stem cells. Cell Death Discov 2021; 7:220. [PMID: 34446696 PMCID: PMC8390744 DOI: 10.1038/s41420-021-00575-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 03/25/2021] [Accepted: 04/23/2021] [Indexed: 12/11/2022] Open
Abstract
Long noncoding RNAs (lncRNAs) are implicated tumor development in a range of different cancers, including pancreatic cancer (PC). Cancer stem cells (CSCs), a drug-resistant cancer cell subset, drive tumor progression in PC. In this work, we aimed to investigate the mechanism by which lncRNA LINC00261 affects the biological functions of CSCs during the progression of PC. Microarray analysis of differentially expressed genes and lncRNAs suggested that LINC00261 is downregulated in PC. Both LINC00261 and ITIH5 were confirmed to be downregulated in PC cells and PC stem cells. Gain-of-function and loss-of-function investigations were performed to analyze their effects on cell proliferation, drug resistance, cell cycle distribution, self-renewal, invasion, and ultimately overall tumorigenicity. These experiments revealed that the expression of stem cell markers was reduced, and cell proliferation, self-renewal ability, cell invasion, drug resistance, and tumorigenicity were all suppressed by upregulation of LINC00261 or ITIH5. The results of dual-luciferase reporter gene, ChIP, and RIP assays indicated that LINC00261 binds directly to GATA6, increasing its activity at the ITIH5 promoter. The presence of LINC00261 and GATA6 inhibited the self-renewal and tumorigenesis of PC stem cells, while silence of ITIH5 rescued those functions. Collectively, this study identifies the tumor suppressive activity of LINC00261 in PC, showing that this lncRNA limits the functions of PC stem through an ITIH5/GATA6 regulatory pathway.
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Seyed Hosseini E, Nikkhah A, Sotudeh A, Alizadeh Zarei M, Izadpanah F, Nikzad H, Haddad Kashani H. The impact of LncRNA dysregulation on clinicopathology and survival of pancreatic cancer: a systematic review and meta-analysis (PRISMA compliant). Cancer Cell Int 2021; 21:447. [PMID: 34425840 PMCID: PMC8383355 DOI: 10.1186/s12935-021-02125-1] [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: 12/08/2020] [Accepted: 07/30/2021] [Indexed: 12/26/2022] Open
Abstract
Purpose An increasing number of studies have reported a significant association between long non-coding RNAs (lncRNAs) dysregulation and pancreatic cancers. In the present study, we aimed to gather articles to evaluate the prognostic value of long non coding RNA in pancreatic cancer. Experimental design We systematically searched all eligible articles from databases of PubMed, Web of Science, and Scopus to meta-analysis of published articles and screen association of multiple lncRNAs expression with clinicopathology and/or survival of pancreatic cancer. The pooled hazard ratios (HRs) and their 95% confidence intervals (95% CIs) were used to analysis of overall survival, disease-free survival and progression-free survival were measured with a fixed or random effects model. Results A total of 39 articles were included in the present meta-analysis. Our results showed that dysregulation of lncRNAs were linked to overall survival (39 studies, 4736 patients HR = 0.41, 95% CI 0.25 ± 0.58, random-effects in pancreatic cancer. Moreover, altered lncRNAs were also contributed to progression-free survival (8 studies, 1180 patients HR: 1.88, 95% CI (1.35–2.62) and disease-free survival (2 studies, 285 patients, HR: 6.07, 95% CI 1.28–28.78). In addition, our findings revealed the association between dysregulated RNAs and clinicopathological features in this type of cancer. Conclusions In conclusion, dysregulated lncRNAs could be served as promising biomarkers for diagnosis and prognosis of pancreatic cancer.
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Affiliation(s)
- Elahe Seyed Hosseini
- Gametogenesis Research Center, Kashan University of Medical Science, Kashan, Iran.,Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Ali Nikkhah
- Student Research Committee, Kashan University of Medical Science, Kashan, Iran
| | - Amir Sotudeh
- Student Research Committee, Kashan University of Medical Science, Kashan, Iran
| | - Marziyeh Alizadeh Zarei
- Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Fatemeh Izadpanah
- Food and Drug Laboratory Research Center and Food and Drug Reference Control Laboratories Center, Food & Drug Administration of Iran, MOH & ME, Tehran, Iran
| | - Hossein Nikzad
- Gametogenesis Research Center, Kashan University of Medical Science, Kashan, Iran.,Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Hamed Haddad Kashani
- Gametogenesis Research Center, Kashan University of Medical Science, Kashan, Iran. .,Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.
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Yin Y, Zhang J, Yu H, Liu M, Zheng X, Zhou R. Effect of lncRNA-ATB/miR-651-3p/Yin Yang 1 pathway on trophoblast-endothelial cell interaction networks. J Cell Mol Med 2021; 25:5391-5403. [PMID: 33942988 PMCID: PMC8184718 DOI: 10.1111/jcmm.16550] [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: 12/07/2020] [Revised: 03/23/2021] [Accepted: 03/30/2021] [Indexed: 12/14/2022] Open
Abstract
Our previous studies have confirmed that lncRNA‐ATB may be involved in the pathogenesis of preeclampsia, however, it is uncertain whether lncRNA‐ATB influence the interaction between trophoblast and endothelial cells, which is crucial to the uterine spiral artery remodelling. Scratch wound healing and transwell invasion assay were conducted to test the migration and invasion of trophoblast cells. Co‐culture model was used to simulate the physiological environment in vivo. The expression levels of lncRNA‐ATB were analyzed in placenta tissues from healthy pregnant women and preeclampsia patients. Subsequently, the binding site of lncRNA‐ATB and miR‐651‐3p was verified using dual‐luciferase reporter assay, and the rescue experiment was used to study the effects of these two on the biological function. The direct effects of miR‐651‐3p and Yin Yang 1 (YY1) were verified using similar methods. LncRNA‐ATB was found to be down‐regulated in the placenta of preeclampsia patients. LncRNA‐ATB knockdown decreased trophoblast migration, invasion and colocalisation with human umbilical vein endothelial cells. MiR‐651‐3p was a direct target of lncRNA‐ATB and they had opposite effects. Moreover, the expression of lncRNA‐ATB and miR‐651‐3p in placental tissues was negatively correlated. MiR‐651‐3p has been confirmed to directly target the 3′ untranslated region of YY1. The inhibitory effects of YY1 low expression on biological function was rescued by miR‐651‐3p depletion. Western blot analysis showed that lncRNA‐ATB could regulate YY1 expression by sponging miR‐651‐3p. LncRNA‐ATB functioned as a competitive endogenous RNA of miR‐651‐3p to regulate YY1 on progress of spiral artery remodelling.
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Affiliation(s)
- Yangxue Yin
- Department of Obstetrics and Gynecology, Center for Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University) of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Jiashuo Zhang
- Department of Obstetrics and Gynecology, Center for Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University) of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Hongbiao Yu
- Department of Obstetrics and Gynecology, Center for Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University) of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Min Liu
- Department of Obstetrics and Gynecology, Center for Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University) of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Xuelian Zheng
- Laboratory of Molecular Translational Medicine, Center for Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Rong Zhou
- Department of Obstetrics and Gynecology, Center for Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University) of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China
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Falahati Z, Mohseni-Dargah M, Mirfakhraie R. Emerging Roles of Long Non-coding RNAs in Uterine Leiomyoma Pathogenesis: a Review. Reprod Sci 2021; 29:1086-1101. [PMID: 33844188 DOI: 10.1007/s43032-021-00571-w] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 04/01/2021] [Indexed: 01/19/2023]
Abstract
Uterine leiomyoma (UL), as the most prevalent type of women's health disorders, is a benign tumor that originates from the smooth muscle cell layer of the uterus. A great number of associated complications are observed including infertility, miscarriage, bleeding, pain, dysmenorrhea, menorrhagia, and dyspareunia. Although the etiology of UL is largely undefined, environmental and genetic factors are witnessed to engage in the UL development. As long non-coding RNAs (lncRNAs) are involved in various types of cellular functions, in recent years, a great deal of attention has been drawn to them and their possible roles in UL pathogenesis. Moreover, they have illustrated their potential to be promising candidates for UL treatment. In this review paper, firstly, an overview of UL pathogenesis is presented. Then, the regulation of lncRNAs in UL and their possible mechanisms in cancer development are reviewed. Eventually, therapeutic approaches targeting lncRNAs in various cancers and UL are explored.
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Affiliation(s)
- Zahra Falahati
- Department of Biological Sciences, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan, Iran
| | - Masoud Mohseni-Dargah
- Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
- School of Engineering, Faculty of Science and Engineering, Macquarie University, Sydney, Australia
| | - Reza Mirfakhraie
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Koodakyar St., Velenjak Ave, Chamran Highway, Tehran, Iran.
- Genomic Research Centre, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Yue P, Bao J. Prognostic Value of Long Non-Coding RNA Long Intergenic Non-Protein Coding RNA 1586 in Pancreatic Cancer. J BIOMATER TISS ENG 2021. [DOI: 10.1166/jbt.2021.2414] [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
This study investigated the prognostic value of the long non-coding RNA (lncRNA) LINC01586 in pancreatic cancer. Three pancreatic cancer patients who received pancreaticoduodenectomies in our department in January 2019 were retrospectively selected. Cancer tissue and adjacent tissue
samples were collected for high-throughput sequencing of lncRNAs. Among them, 221 lncRNAs were up-regulated and 235 were down-regulated. The expression of LINC01586 was decreased in pancreatic cancer patients (logFC = -3.308). An additional 74 tissue specimens were collected from pancreatic
cancer patients from January 2011 to December 2016 for low-throughput validation. Patient samples were categorized into overexpression and low expression groups, based on the median LINC01586 expression level. The LINC01586 low expression group exhibited larger tumor size than the overexpression
group (P < 0.001), while the low expression group exhibited a lower cancer-related survival rate than the overexpression group (one-year cancer-related survival rate: 55.6% vs. 89.2%, P < 0.001). Further analysis confirmed that low expression of LINC01586 was associated
with poor prognosis for pancreatic cancer patients (OR = 0.169, 95% CI 0.066-0.437, P = 0.000). KEGG signaling pathway analysis was used to enrich LINC01586 target genes, and were mainly related to two metabolic pathways: insulin secretion (P = 0.011) and dopaminergic synapses
(P = 0.0129), with SNAP25 as the core gene. The expression of LINC01586 and SNAP25were positively correlated in pancreatic cancer (R = 0.81 and P < 0.001). Together, our results indicate that LINC01586 may be used as a biomarker for prognosis predictions
in pancreatic cancer patients, and its low expression is associated with poor prognosis.
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Affiliation(s)
- Pengju Yue
- Department of General Surgery, Chengdu First People’s Hospital, Chengdu 610041, Sichuan, PR China
| | - Jing Bao
- Department of General Surgery, Chengdu First People’s Hospital, Chengdu 610041, Sichuan, PR China
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Abstract
Osteoarthritis (OA), one of the most common motor system disorders, is a degenerative disease involving progressive joint destruction caused by a variety of factors. At present, OA has become the fourth most common cause of disability in the world. However, the pathogenesis of OA is complex and has not yet been clarified. Long non-coding RNA (lncRNA) refers to a group of RNAs more than 200 nucleotides in length with limited protein-coding potential, which have a wide range of biological functions including regulating transcriptional patterns and protein activity, as well as binding to form endogenous small interference RNAs (siRNAs) and natural microRNA (miRNA) molecular sponges. In recent years, a large number of lncRNAs have been found to be differentially expressed in a variety of pathological processes of OA, including extracellular matrix (ECM) degradation, synovial inflammation, chondrocyte apoptosis, and angiogenesis. Obviously, lncRNAs play important roles in regulating gene expression, maintaining the phenotype of cartilage and synovial cells, and the stability of the intra-articular environment. This article reviews the results of the latest research into the role of lncRNAs in a variety of pathological processes of OA, in order to provide a new direction for the study of OA pathogenesis and a new target for prevention and treatment. Cite this article: Bone Joint Res 2021;10(2):122-133.
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Affiliation(s)
- Chao Peng He
- Department of Orthopedics, The Second Affiliated Hospital, Hunan Normal University, Hunan, China
| | - Xin Chen Jiang
- Department of Orthopedics, The Second Affiliated Hospital, Hunan Normal University, Hunan, China
| | - Cheng Chen
- Department of Orthopedics, The Second Affiliated Hospital, Hunan Normal University, Hunan, China
| | - Hai Bin Zhang
- Department of Orthopedics, The Xiangya Hospital of Central South University Changsha, Hunan, China
| | - Wen Dong Cao
- Department of Orthopedics, The Second Affiliated Hospital, Hunan Normal University, Hunan, China
| | - Qi Wu
- Department of Orthopedics, The Second Affiliated Hospital, Hunan Normal University, Hunan, China
| | - Chi Ma
- Department of Orthopedics, The First Affiliated Hospital (People’s Hospital of Xiangxi Autonomous Prefecture), Jishou University, Jishou, China
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Ge JN, Yan D, Ge CL, Wei MJ. LncRNA C9orf139 can regulate the growth of pancreatic cancer by mediating the miR-663a/Sox12 axis. World J Gastrointest Oncol 2020; 12:1272-1287. [PMID: 33250960 PMCID: PMC7667452 DOI: 10.4251/wjgo.v12.i11.1272] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 09/24/2020] [Accepted: 10/12/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Recent studies have proved the important role of many oncogenic long non-coding RNAs (lncRNAs) in the progression of pancreatic cancer, but little is known about the mechanisms of tumor suppression in pancreatic cancer. AIM To evaluate the function of tumor suppressor lncRNA C9orf139 in pancreatic cancer progression and to study the underlying mechanism. METHODS We assigned 54 patients with pancreatic ductal adenocarcinoma treated at our hospital to the patient group and 30 normal subjects undergoing physical examination to the control group. RT-qPCR was used to measure the relative expression of C9orf139 in the tissue and serum of patients, in an attempt to investigate the prognostic value of C9orf139 in pancreatic cancer patients. The luciferase reporter gene assay was performed to determine the interaction between C9orf139 and miR-663a. The biological function of C9orf139 was assessed by in vitro assays and in vivo subcutaneous tumor formation tests in animal models. To figure out the molecular mechanism of C9orf139 to act on miR-663a/Sox12, RNA pull-down, Western blot assay, RNA immunoprecipitation assay, and co-immunoprecipitation assay were performed. RESULTS C9orf139 level significantly increased in the tissue and serum of patients, which had clinical diagnostic value for pancreatic cancer. Patients with high C9orf139 expression had a higher risk of progressing to stage III + IV, lymph node metastasis, and poor differentiation. Cox regression analysis suggested that C9orf139, tumor-node-metastasis stage, and lymph node metastasis were independent prognostic factors in patients. The underlying mechanism of C9orf139 was that it promoted the growth of pancreatic cancer cells by modulating the miR-663a/Sox12 axis. CONCLUSION C9orf139 is highly expressed in pancreatic cancer, qualified to be used as a potential diagnostic and prognostic marker for pancreatic cancer. Its promotion of pancreatic cancer cell growth is achieved by mediating the miR-663a/Sox12 axis.
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Affiliation(s)
- Jin-Nian Ge
- Department of General Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Di Yan
- Intensive Care Unit, The Central Affiliated Hospital of Shenyang Medical College, Shenyang 110024, Liaoning Province, China
| | - Chun-Lin Ge
- Department of General Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Min-Jie Wei
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang 110122, Liaoning Province, China
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Xue Y, Zhong Y, Wu T, Sheng Y, Dai Y, Xu L, Bao C. Anti-Proliferative and Apoptosis-Promoting Effect of microRNA-125b on Pancreatic Cancer by Targeting NEDD9 via PI3K/AKT Signaling. Cancer Manag Res 2020; 12:7363-7373. [PMID: 32903925 PMCID: PMC7445537 DOI: 10.2147/cmar.s227315] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2019] [Accepted: 01/28/2020] [Indexed: 12/22/2022] Open
Abstract
PURPOSE The expression of microRNA-125b (miR-125b) is low in a variety of cancers, including gastric, lung, bladder, thyroid, and esophageal cancers. However, its specific mechanism in pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study is aimed to explore the role of miR-125b in PDAC. METHODS PDAC tissues and adjacent tissues were collected for miR-125b analysis by qRT-PCR. Different PDAC cell lines were cultured for miR-125b detection by qRT-PCR, and CAPAN1 cells were selected for the downstream experiments. Cell proliferation was characterized by methyl thiazolyl tetrazolium (MTT) and 5-bromo-2-deoxyUridine (BrdU) staining. Flow cytometry was utilized for apoptosis and cell cycle changes. Cell invasion was determined by the Transwell assay and the dual-luciferase assay was utilized for validating the target gene. Western blotting was used to detect apoptosis related and PI3K/AKT signaling proteins. RESULTS miR-125b was significantly down-regulated in human PDAC tissues and cell lines (P < 0.05). miR-125b inhibited the growth and invasion of CAPAN1 cells, facilitated apoptosis, and blocked the cell cycle at the G0/G1 phase. Furthermore, miR-125 directly targeted NEDD9. The high expression of NEDD9 impaired the anti-proliferative and anti-apoptotic activity of miR-125b. miR-125b also inhibited apoptosis-related proteins and PI3K/AKT signaling pathways via NEDD9. CONCLUSION miR-125b decreased cell growth and invasion, and facilitated apoptosis in CAPAN1 cells through PI3K/AKT inhibition via targeting NEDD9.
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Affiliation(s)
- Yuzheng Xue
- Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi214041, Jiangsu, People’s Republic of China
| | - Yao Zhong
- Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi214041, Jiangsu, People’s Republic of China
| | - Tielong Wu
- Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi214041, Jiangsu, People’s Republic of China
| | - Yingyue Sheng
- Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi214041, Jiangsu, People’s Republic of China
| | - Yuanyuan Dai
- Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi214041, Jiangsu, People’s Republic of China
| | - Lingling Xu
- Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi214041, Jiangsu, People’s Republic of China
| | - Chuanqing Bao
- Department of Gastrointestinal Surgery, Affiliated Hospital of Jiangnan University, Wuxi214041, Jiangsu, People’s Republic of China
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Duan H, Ding X, Luo H. The prognostic value of long noncoding RNA activated by TGF-β in digestive system cancers: A meta-analysis. Medicine (Baltimore) 2020; 99:e21324. [PMID: 32791727 PMCID: PMC7387048 DOI: 10.1097/md.0000000000021324] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND To systematically evaluate whether the expression level of long non-coding RNA activated by transforming growth factor-β (lncRNA-ATB) is correlated with the prognosis of digestive system cancer (DSC) patients. METHODS PubMed, Embase, Cochrane Library, Web of Science, Springerlink, Nature, and Karger databases were searched up to April 20, 2019 by 2 experienced researchers independently. The quality of studies was assessed with the Newcastle-Ottawa scale. The Review Manager 5.2 and STATA 12.0 software were used for this meta-analysis. RESULT Eleven studies with 1227 DSC patients were included in the meta-analysis. Except for pancreatic cancer, high expression of lncRNA-ATB was associated with lymph node metastasis (risk ratio (RR) = 1.26, 95% confidence interval (CI): 1.12-1.42, P < .001), advanced clinical staging (RR = 1.44, 95%CI: 1.23-1.69, P < .001), reduced overall survival rate (OS) (hazard ratio (HR) = 2.33, 95%CI: 1.22-4.50, P = .01), and recurrence-free survival (RFS) (HR = 2.61, 95%CI: 1.46-4.65, P = .001) compared with low lncRNA-ATB expression in DSCs. CONCLUSIONS High expression of lncRNA-ATB was significantly correlated with poor prognosis for most DSCs. The expression level of lncRNA-ATB could be a promising prognostic biomarker for DSC patients.
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Cheng XB, Fu B, Li XZ, Jiang Y. Prognostic value of long non-coding RNA ATB in digestive system cancers: A meta-analysis. Pathol Res Pract 2020; 216:152949. [PMID: 32307201 DOI: 10.1016/j.prp.2020.152949] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2020] [Revised: 03/09/2020] [Accepted: 03/29/2020] [Indexed: 12/19/2022]
Abstract
BACKGROUND The present meta-analysis has evaluated the association between lncRNA ATB, prognosis and clinicopathological parameters in patients with digestive cancers. METHODS Eligible studies were gathered from Web of Science, PubMed, Embase, Cochrane Library, WanFang databases and China National Knowledge Infrastructure (up to October 15, 2019). Hazard ratios (HRs) and 95 % confidence intervals (CIs) were calculated to estimate the prognosis and clinicopathological parameters of lncRNA ATB in patients with digestive cancers. RESULT We divided this study into two groups, pancreatic cancer (PC, downregulation) and non-pancreatic cancer (non-PC, upregulation). In the non-PC group, high expression levels of lncRNA ATB were significantly related to poor OS (pooled HR = 2.19, 95 % CI 1.68-2.85, P＜0.00001). In contrast, increased levels of lncRNA ATB in pancreatic cancer tissue were favorable factors in OS (HR = 0.47, 95 % CI 0.32-0.69, P = 0.0001). The pooled data suggested that high expression levels of lncRNA ATB predicted a poor DFS in CRC and a poor RFS in HCC. Increased expression of lncRNA ATB was correlated with negative lymph node metastasis and TNM stage in the non-PC group. In contrast, lncRNA ATB were favorable factors for LNM and TNM stages in pancreatic cancer. CONCLUSION LncRNA ATBs, whether cancer promoters or suppressors, were potential biomarkers and therapeutic targets for digestive system cancers.
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Affiliation(s)
- Xian-Bin Cheng
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Jilin Province, China
| | - Bo Fu
- Department of General Surgery, Taihe County People's Hospital, Anhui Province, China
| | - Xing-Zhao Li
- Department of Ultrasound, China-Japan Union Hospital of Jilin University, Jilin Province, China
| | - Yang Jiang
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Jilin Province, China.
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LncRNA-ATB in cancers: what do we know so far? Mol Biol Rep 2020; 47:4077-4086. [PMID: 32248383 DOI: 10.1007/s11033-020-05415-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Accepted: 03/30/2020] [Indexed: 01/06/2023]
Abstract
Cancer-related deaths did not apparently decrease in the past decades despite aggressive treatments. It's reported that cancer will become the leading cause of death worldwide in the twenty-first century. Increasing evidence has revealed that lncRNAs will emerge as promising cancer biomarkers or therapeutic targets in cancer treatment. LncRNA-ATB, a long noncoding RNA activated by TGF-β, was found to be abnormally expressed in certain cancers and participate in the development and progression of tumors. In addition, aberrant lncRNA-ATB expression was also associated with clinical characteristics of tumors. The purpose of this review is to summarize functions and underlying mechanisms of lncRNA-ATB in tumors, and discuss whether lncRNA-ATB can be a biomarker and therapeutic target in cancers.
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Prognostic impact of lncRNA-ATB expression in malignant solid tumors: A meta-analysis. Pathol Res Pract 2020; 216:152897. [PMID: 32146004 DOI: 10.1016/j.prp.2020.152897] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Revised: 01/27/2020] [Accepted: 02/16/2020] [Indexed: 01/11/2023]
Abstract
PURPOSE Numerous studies have reported the prognostic role of lncRNA-ATB high expression in solid tumours, but its prognostic effect is still uncertain. Therefore, the purpose of this meta-analysis was to further comprehensively verify the prognostic role of the lncRNA-ATB high expression in solid tumours. METHODS A literature search was performed using the electronic platforms to obtain relevant research studies published up to 31 May 2019. Confidence intervals of research endpoints in each study were extracted and merged. All data analysis was performed using Stata12.0 software. RESULTS A total of 2120 patients with solid cancers in 14 studies were enrolled in our meta-analysis eventually. The analysis results revealed that high expression of lncRNA-ATB was related to lower OS (HR:1.46, P < 0.001), shorter DFS(HR:1.73, P < 0.001), and earlier RFS (HR:2.67, P < 0.001). Besides, the high expression of lncRNA-ATB has a considerable risk of lymph node metastasis (OR:2.13, P = 0.017)and perineural invasion (OR:1.58, P = 0.018). CONCLUSIONS Meta-analysis showed that the high lncRNA-ATB expression was a poor prognostic marker in multiple cancer types. The high expression of lncRNA-ATB symbolizes the high risk of lymph node metastasis and perineural invasion in cancer patients.
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Li J, Xia R, Liu T, Cai X, Geng G. LncRNA-ATB Promotes Lung Squamous Carcinoma Cell Proliferation, Migration, and Invasion by Targeting microRNA-590-5p/NF90 Axis. DNA Cell Biol 2020; 39:459-473. [PMID: 31934791 DOI: 10.1089/dna.2019.5193] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Lung cancer with highest morbidity and mortality seriously threatens human health worldwide. Long noncoding RNAs (lncRNAs) exert important biological functions by acting as microRNA, which is implicated in tumorigenesis and cancer development. Previous work has reported that lncRNA-ATB expression was significantly upregulated in lung adenocarcinoma tissues and promoted tumor progression; however, the mechanisms of lncRNA-ATB in lung squamous carcinoma (LSC) are still fairly elusive. In our study, lncRNA-ATB expression also markedly increases in LSC tissues and cell lines in comparison to the adjacent normal tissues and normal lung epithelial cells, respectively. Functional experiments indicate that lncRNA-ATB overexpression improves the proliferative, migratory, and invasive capabilities of normal lung epithelial cells compared with control group. Furthermore, the migratory and invasive abilities are strikingly inhibited in lncRNA-ATB silenced LSC cells. Mechanistically, lncRNA-ATB directly binds to microRNA-590-5p and downregulates microRNA-590-5p level, leading to the upregulation of NF-90 expression. In addition, lncRNA-ATB overexpression promotes the epithelial-mesenchymal transition process, where lncRNA-ATB overexpression facilitates the expression of mesenchymal phenotype related molecules N-cadherin and vimentin, while restrains the expression of epithelial phenotype related proteins E-cadherin and CK-19, compared to the control. Conversely, microRNA-590-5p mimics can reverse the results caused by lncRNA-ATB overexpression. Taken together, our initial data suggest that lncRNA-ATB overexpression may promote the progression of LSC by modulating the microRNA-590-5p/NF-90 axis.
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Affiliation(s)
- Jiayi Li
- Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, P.R. China.,Teaching Hospital of Fujian Medical University, Xiamen, P.R. China
| | - Rongmu Xia
- School of Medicine, Xiamen University, Xiamen, P.R. China
| | - Tao Liu
- Department of Medical Oncology, Xiang'an Hospital of Xiamen University, Xiamen, P.R. China
| | - Xuemin Cai
- School of Medicine, Xiamen University, Xiamen, P.R. China
| | - Guojun Geng
- Teaching Hospital of Fujian Medical University, Xiamen, P.R. China.,Department of Thoracic Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, P.R. China
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Ou ZL, Luo Z, Lu YB. Long non-coding RNA HULC as a diagnostic and prognostic marker of pancreatic cancer. World J Gastroenterol 2019; 25:6728-6742. [PMID: 31857775 PMCID: PMC6920662 DOI: 10.3748/wjg.v25.i46.6728] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Revised: 11/18/2019] [Accepted: 11/29/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Long non-coding RNA (lncRNA) is abnormally expressed in various malignant tumors. In recent years, it has been found that IncRNA HULC is increasingly expressed in pancreatic cancer tissues and is involved in the development and progression of pancreatic cancer. However, the clinical value of serum HULC in pancreatic cancer remains unclear, and there are few studies on how HULC regulates the biological function of pancreatic cancer cells.
AIM To determine the value of lncRNA HULC in the diagnosis and prognosis of pancreatic cancer, and its possible biological potential.
METHODS Sixty patients with pancreatic cancer and sixty patients with benign pancreatic diseases admitted to Xiangya Hospital, Central South University were assigned to the pancreatic cancer group and the benign disease group, respectively, and another 60 healthy subjects were enrolled as the normal group during the same period. HULC-siRNA and NC-siRNA were transfected into pancreatic cancer cells. Quantitative real-time polymerase chain reaction was performed to determine the expression of HULC in tissues, serum, and cells. Western Blot was carried out to determine the expression of β-catenin, c-myc, and cyclin D1 in cells, and the cell counting kit-8, flow cytometry, and Transwell assay were conducted to determine the proliferation, apoptosis and invasion of cells.
RESULTS Highly expressed in the tissues and serum of pancreatic cancer patients, HULC showed good clinical value in distinguishing between patients with pancreatic cancer, patients with benign pancreatic diseases and healthy subjects. HULC was related to pathological parameters including tumor size, T staging, M staging and vascular invasion, and the area-under-the-curve for evaluating these four parameters was 0.844, 0.834, 0.928 and 0.818, respectively. Patients with low expression of HULC had a significantly higher 3-year overall survival (OS) and 5-year OS than those with high expression. T staging, M staging, vascular invasion, and HULC were independent prognostic factors affecting the 3-year OS of patients with pancreatic cancer. Inhibition of HULC expression prevented the proliferation and invasion of pancreatic cancer cells, promoted apoptosis, and inhibited the expression of Wnt/β-catenin signaling pathway-related proteins, β-catenin, c-myc, and cyclin D1. The Wnt/β-catenin signaling pathway agonist (LiCl) restored proliferation, apoptosis, and invasion of pancreatic cancer cells with inhibited expression of HULC.
CONCLUSION HULC is an effective marker for the diagnosis and prognosis of pancreatic cancer, which may affect the biological function of pancreatic cancer cells through the Wnt/β-catenin signaling pathway.
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Affiliation(s)
- Zheng-Lin Ou
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Zhen Luo
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Ye-Bin Lu
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
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20
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Zhang L, Wang Y, Zhang L, You G, Li C, Meng B, Zhou M, Zhang M. LINC01006 promotes cell proliferation and metastasis in pancreatic cancer via miR-2682-5p/HOXB8 axis. Cancer Cell Int 2019; 19:320. [PMID: 31827394 PMCID: PMC6889337 DOI: 10.1186/s12935-019-1036-2] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2019] [Accepted: 11/15/2019] [Indexed: 02/08/2023] Open
Abstract
Background Pancreatic cancer (PC) is one of the deadliest cancers about the digestive system. Recent researches have validated that long non-coding RNAs (lncRNAs) play vital roles in various cancers, while the function of LINC01006 in PC is rarely clarified. Aim of the study Investigation of the specific role of LINC01006 in PC. Methods LINC01006 expression was examined by RT-qPCR. CCK-8, EdU, transwell, wound healing, and western blot assays were carried out to explore the function of LINC01006 in PC. The interaction among LINC01006, miR-2682-5p and HOXB8 was verified by luciferase reporter, RIP and ChIP assays. Results The expression of LINC01006 was markedly upregulated in PC tissues and cells. Furthermore, LINC01006 knockdown inhibited PC cell proliferation, invasion and migration, and upregulation of LINC01006 led to the opposite results. Besides, miR-2682-5p expression was downregulated and negatively regulated by LINC01006 in PC. Meanwhile, LINC01006 could bind with miR-2682-5p in PC. Moreover, miR-2682-5p negatively regulated HOXB8 expression and there was a binding site between miR-2682-5p and HOXB8 in PC. Additionally, miR-2682-5p overexpression or HOXB8 knockdown rescued the promotive effects of LINC01006 upregulation on PC cell progression. Similarly, miR-2682-5p inhibition or HOXB8 overexpression countervailed the repressive role of LINC01006 downregulation in PC cell progression. In addition, the transcription factor HOXB8 could activate LINC01006 transcription in PC. Conclusions LINC01006 promotes cell proliferation and metastasis in pancreatic cancer via miR-2682-5p/HOXB8 axis, which may facilitate the treatment for PC.
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Affiliation(s)
- Luyang Zhang
- 1Department of Hepatobiliary Surgery, Affiliated of Cancer Hospital of Zhengzhou University, 127 Dongming Road, Zhengzhou, 450008 Henan China
| | - Yunjian Wang
- 1Department of Hepatobiliary Surgery, Affiliated of Cancer Hospital of Zhengzhou University, 127 Dongming Road, Zhengzhou, 450008 Henan China
| | - Ling Zhang
- 1Department of Hepatobiliary Surgery, Affiliated of Cancer Hospital of Zhengzhou University, 127 Dongming Road, Zhengzhou, 450008 Henan China
| | - Guohua You
- 1Department of Hepatobiliary Surgery, Affiliated of Cancer Hospital of Zhengzhou University, 127 Dongming Road, Zhengzhou, 450008 Henan China
| | - Congyu Li
- 2Department of Ultrasonography, Affiliated of Cancer Hospital of Zhengzhou University, Zhengzhou, 450008 Henan China
| | - Bo Meng
- 1Department of Hepatobiliary Surgery, Affiliated of Cancer Hospital of Zhengzhou University, 127 Dongming Road, Zhengzhou, 450008 Henan China
| | - Minghe Zhou
- 1Department of Hepatobiliary Surgery, Affiliated of Cancer Hospital of Zhengzhou University, 127 Dongming Road, Zhengzhou, 450008 Henan China
| | - Min Zhang
- 1Department of Hepatobiliary Surgery, Affiliated of Cancer Hospital of Zhengzhou University, 127 Dongming Road, Zhengzhou, 450008 Henan China
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Wang CZ, Yan GX, Dong DS, Xin H, Liu ZY. LncRNA-ATB promotes autophagy by activating Yes-associated protein and inducing autophagy-related protein 5 expression in hepatocellular carcinoma. World J Gastroenterol 2019; 25:5310-5322. [PMID: 31558875 PMCID: PMC6761242 DOI: 10.3748/wjg.v25.i35.5310] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Revised: 07/30/2019] [Accepted: 08/07/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Long non-coding RNAs (lncRNAs) play important roles in many diseases, including hepatocellular carcinoma (HCC). Autophagy is a metabolic pathway that facilitates cancer cell survival in response to stress. The relationship between autophagy and the lncRNA-activated by transforming growth factor beta (lncRNA-ATB) in HCC remains unknown.
AIM To explore the influence of lncRNA-ATB in regulating autophagy in HCC cells and the underlying mechanism.
METHODS In the present study, we evaluated lncRNA-ATB expression in tumor and adjacent non-tumor tissues from 72 HCC cases by real-time PCR. We evaluated the role of lncRNA-ATB in the proliferation and clonogenicity of HCC cells in vitro. The effect of lncRNA-ATB on autophagy was determined using a LC3-GFP reporter and transmission electron microscopy. Furthermore, the mechanism by which lncRNA-ATB regulates autophagy was explored by immunofluorescence staining, RNA immunoprecipitation (RIP), and Western blot.
RESULTS The expression of lncRNA-ATB was higher in HCC tissues than in normal liver tissues, and lncRNA-ATB expression was positively correlated with tumor size, TNM stage, and poorer survival of patients with HCC. Moreover, ectopic overexpression of lncRNA-ATB promoted cell proliferation and clonogenicnity of HCC cells in vitro. LncRNA-ATB promoted autophagy by activating Yes-associated protein (YAP). Moreover, lncRNA-ATB interacted with autophagy-related protein 5 (ATG5) mRNA and increased ATG5 expression.
CONCLUSION LncRNA-ATB regulates autophagy by activating YAP and increasing ATG5 expression. Our data demonstrate a novel function for lncRNA-ATB in autophagy and suggest that lncRNA-ATB plays an important role in HCC.
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Affiliation(s)
- Chuan-Zhuo Wang
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Guang-Xin Yan
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - De-Shuo Dong
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - He Xin
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Zhao-Yu Liu
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
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HOXA11-AS promotes the migration and invasion of hepatocellular carcinoma cells by inhibiting miR-124 expression by binding to EZH2. Hum Cell 2019; 32:504-514. [DOI: 10.1007/s13577-019-00269-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Accepted: 06/29/2019] [Indexed: 12/19/2022]
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Gao Z, Zhou H, Wang Y, Chen J, Ou Y. Regulatory effects of lncRNA ATB targeting miR-200c on proliferation and apoptosis of colorectal cancer cells. J Cell Biochem 2019; 121:332-343. [PMID: 31222825 DOI: 10.1002/jcb.29180] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Revised: 05/22/2019] [Accepted: 05/23/2019] [Indexed: 01/17/2023]
Abstract
This investigation was intended to elucidate whether long noncoding RNA (lncRNA)-activated by transforming growth factor-β (ATB) interacting with miR-200c could mediate colorectal cancer (CRC) progression, offering potential strategies for diagnosing and treating CRC. Here totally 315 patients with CRC were recruited, and their CRC tissues and adjacent normal tissues were gathered. Concurrently, four colon cancer cell lines (ie, SW620, Lovo, HCT116, and SW480) and the human colon mucosal epithelial cell line (NCM460) were also purchased. Moreover, si-ATB, si-NC, miR-200c mimic, miR-200c inhibitor, and miR-NC were prepared for transfection into the CRC cells, and their effects on CRC cell lines were evaluated based on the conduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony formation assay, and flow cytometry assay. Eventually, the Luciferase reporter gene assay was carried out to judge if there existed a targeted relationship between ATB and miR-200c. The results of Cox regression analyses suggested that overexpressed lncRNA ATB, underexpressed miR-200c, poor tumor differentiation, lymph-vascular invasion, and perineural invasion were symbolic of shortened survival of the patients with CRC (all P < .05). Besides, transfection of pcDNA3.1-ATB and miR-200c inhibitor could boost the viability and proliferation of Lovo and SW620 cell lines (all P < .05). Meanwhile, the expressions of p53 and p21 were also reduced under treatments of pcDNA3.1-ATB and miR-200c inhibitor (P < .05). In addition, CDK2 seemed to reverse the contribution of miR-200c to intensifying viability and proliferation of Lovo and SW420 cell lines (P < .05). Furthermore, ATB might downregulate miR-200c expression by targeting it (P < .05), and CDK2 was subjected to dual regulation of both ATB and miR-200c (P < .05). In conclusion, the lncRNA ATB/miR-200c/CDK2 signaling was responsible for intensified proliferation and prohibited apoptosis of CRC cells, which might provide effective approaches for diagnosing and treating CRC.
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Affiliation(s)
- Zhenyuan Gao
- Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China
| | - Hairong Zhou
- Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China
| | - Yaping Wang
- Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China
| | - Juan Chen
- Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China
| | - Yimei Ou
- Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China
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Hao Y, Baker D, Ten Dijke P. TGF-β-Mediated Epithelial-Mesenchymal Transition and Cancer Metastasis. Int J Mol Sci 2019; 20:ijms20112767. [PMID: 31195692 PMCID: PMC6600375 DOI: 10.3390/ijms20112767] [Citation(s) in RCA: 768] [Impact Index Per Article: 128.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Revised: 05/21/2019] [Accepted: 05/24/2019] [Indexed: 02/07/2023] Open
Abstract
Transforming growth factor β (TGF-β) is a secreted cytokine that regulates cell proliferation, migration, and the differentiation of a plethora of different cell types. Consistent with these findings, TGF-β plays a key role in controlling embryogenic development, inflammation, and tissue repair, as well as in maintaining adult tissue homeostasis. TGF-β elicits a broad range of context-dependent cellular responses, and consequently, alterations in TGF-β signaling have been implicated in many diseases, including cancer. During the early stages of tumorigenesis, TGF-β acts as a tumor suppressor by inducing cytostasis and the apoptosis of normal and premalignant cells. However, at later stages, when cancer cells have acquired oncogenic mutations and/or have lost tumor suppressor gene function, cells are resistant to TGF-β-induced growth arrest, and TGF-β functions as a tumor promotor by stimulating tumor cells to undergo the so-called epithelial-mesenchymal transition (EMT). The latter leads to metastasis and chemotherapy resistance. TGF-β further supports cancer growth and progression by activating tumor angiogenesis and cancer-associated fibroblasts and enabling the tumor to evade inhibitory immune responses. In this review, we will consider the role of TGF-β signaling in cell cycle arrest, apoptosis, EMT and cancer cell metastasis. In particular, we will highlight recent insights into the multistep and dynamically controlled process of TGF-β-induced EMT and the functions of miRNAs and long noncoding RNAs in this process. Finally, we will discuss how these new mechanistic insights might be exploited to develop novel therapeutic interventions.
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Affiliation(s)
- Yang Hao
- Department of Cell and Chemical Biology and Oncode Institute, Leiden University Medical Center, Einthovenweg 20, 2300 RC Leiden, The Netherlands.
| | - David Baker
- Department of Cell and Chemical Biology and Oncode Institute, Leiden University Medical Center, Einthovenweg 20, 2300 RC Leiden, The Netherlands.
| | - Peter Ten Dijke
- Department of Cell and Chemical Biology and Oncode Institute, Leiden University Medical Center, Einthovenweg 20, 2300 RC Leiden, The Netherlands.
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Long non-coding RNA activated by transforming growth factor beta alleviates lipopolysaccharide-induced inflammatory injury via regulating microRNA-223 in ATDC5 cells. Int Immunopharmacol 2019; 69:313-320. [PMID: 30771739 DOI: 10.1016/j.intimp.2019.01.056] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Revised: 01/29/2019] [Accepted: 01/31/2019] [Indexed: 12/13/2022]
Abstract
Osteoarthritis (OA) is a conversant joint disease, which seriously threatens the health of the elderly, and even leads to disability. Long non-coding RNA-activated by transforming growth factor beta (lncRNA-ATB) has been reported in diverse cancers. However, the functions of lncRNA-ATB in OA remain uninvestigated. The current study aimed to explore the impacts of lncRNA-ATB on lipopolysaccharide (LPS)-induced inflammatory injury in ATDC5 cells and to uncover the underlying mechanism. LPS-induced ATDC5 cell injury model was constructed, and the effects of lncRNA-ATB on LPS-injured cells were explored via analyzing cell viability, apoptosis, iNOS, COX-2, and inflammatory cytokines (IL-6 and TNF-α). Subsequently, the relationship between lncRNA-ATB and microRNA (miR)-223 was detected, and whether miR-223 was involved in modulating LPS-induced cells injury in ATDC5 cells was investigated. Finally, MyD88/NF-κB and p38MAPK pathways were assessed to explore the underlying mechanism. Results showed that LPS repressed cell viability, induced apoptosis, and promoted iNOS, COX-2, IL-6 and TNF-α expression. Additionally, we observed that lncRNA-ATB expression was down-regulated in LPS-injured cells, and lncRNA-ATB overexpression significantly alleviated LPS-induced inflammatory injury in ATDC5 cells. Interesting results revealed that miR-223 expression was down-regulated by lncRNA-ATB and miR-223 overexpression declined the protective effect of lncRNA-ATB on LPS-injured ATDC5 cells. Further, the signaling pathway experiments showed that lncRNA-ATB inhibited MyD88/NF-κB and p38MAPK pathways by down-regulating miR-223 in LPS-injured cells. These data demonstrated that lncRNA-ATB protected ATDC5 cells against LPS-induced inflammatory injury by repressing MyD88/NF-κB and p38MAPK pathways, which was mediated by down-regulation of miR-223.
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Li RH, Chen M, Liu J, Shao CC, Guo CP, Wei XL, Li YC, Huang WH, Zhang GJ. Long noncoding RNA ATB promotes the epithelial-mesenchymal transition by upregulating the miR-200c/Twist1 axe and predicts poor prognosis in breast cancer. Cell Death Dis 2018; 9:1171. [PMID: 30518916 PMCID: PMC6281614 DOI: 10.1038/s41419-018-1210-9] [Citation(s) in RCA: 56] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2018] [Revised: 10/27/2018] [Accepted: 11/05/2018] [Indexed: 02/05/2023]
Abstract
Recent studies indicate that the long noncoding RNA ATB (lncATB) can induce the epithelial−mesenchymal transition (EMT) in cancer cells, but the specific cellular targets of lncATB require further investigation. In the present study, the upregulation of lncATB in breast cancer cells was validated in a TGF-β-induced EMT model. Gain- and loss-of-function studies demonstrated that lncATB enhanced cell migration, invasion and clonogenicity in vitro and in vivo. LncATB promoted the EMT by acting as a sponge for the miR-200 family and restoring Twist1 expression. Subsequently, the clinical significance of lncATB was investigated in a cohort of breast cancer patients (N = 131). Higher lncATB expression was correlated with increased nodal metastasis (P = 0.036) and advanced clinical stage (P = 0.011) as well as shorter disease-free survival (P = 0.043) and overall survival (P = 0.046). These findings define Twist1 as a major target of lncATB in the induction of the EMT and highlight lncATB as a biomarker in breast cancer patients.
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Affiliation(s)
- Rong-Hui Li
- ChangJiang Scholar's Laboratory, Shantou University Medical College (SUMC), 515041, Shantou, Guangdong, China
| | - Min Chen
- ChangJiang Scholar's Laboratory, Shantou University Medical College (SUMC), 515041, Shantou, Guangdong, China.,The Cancer Center, Xiang'an Hospital of Xiamen University, 2000 East Xiang'an Rd., Xiang'an, Xiamen, China
| | - Jing Liu
- ChangJiang Scholar's Laboratory, Shantou University Medical College (SUMC), 515041, Shantou, Guangdong, China
| | - Chang-Chun Shao
- ChangJiang Scholar's Laboratory, Shantou University Medical College (SUMC), 515041, Shantou, Guangdong, China
| | - Cui-Ping Guo
- The Breast Center, The Cancer Hospital of SUMC, 515041, Shantou, Guangdong, China
| | - Xiao-Long Wei
- Department of Pathology, The Cancer Hospital of SUMC, Shantou, Guangdong, China
| | - Yao-Chen Li
- ChangJiang Scholar's Laboratory, Shantou University Medical College (SUMC), 515041, Shantou, Guangdong, China
| | - Wen-He Huang
- The Breast Center, The Cancer Hospital of SUMC, 515041, Shantou, Guangdong, China
| | - Guo-Jun Zhang
- ChangJiang Scholar's Laboratory, Shantou University Medical College (SUMC), 515041, Shantou, Guangdong, China. .,The Cancer Center, Xiang'an Hospital of Xiamen University, 2000 East Xiang'an Rd., Xiang'an, Xiamen, China.
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Suppression of lncRNA-ATB prevents amyloid-β-induced neurotoxicity in PC12 cells via regulating miR-200/ZNF217 axis. Biomed Pharmacother 2018; 108:707-715. [DOI: 10.1016/j.biopha.2018.08.155] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2018] [Revised: 08/23/2018] [Accepted: 08/28/2018] [Indexed: 11/23/2022] Open
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Dang X, Lian L, Wu D. The diagnostic value and pathogenetic role of lncRNA-ATB in patients with osteoarthritis. Cell Mol Biol Lett 2018; 23:55. [PMID: 30505322 PMCID: PMC6258155 DOI: 10.1186/s11658-018-0118-9] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2018] [Accepted: 10/15/2018] [Indexed: 12/20/2022] Open
Abstract
Background In view of the roles of long non-coding RNAs (lncRNAs) in human diseases and the high incidence of osteoarthritis, we investigated the role of long non-coding RNA activated by transforming growth factor-β (lncRNA-ATB) in osteoarthritis and explored its diagnostic value for this disease. Methods The study involved 98 patients with osteoarthritis and 76 healthy subjects. Blood was extracted from each participant and the expression of lncRNA-ATB in the serum was detected using quantitative Real Time -PCR. ROC curve analysis was performed to evaluate the diagnostic value of lncRNA-ATB for osteoarthritis. Based on the median serum level of lncRNA-ATB, patients were divided into a high-level group and a low-level group. Correlations between the serum levels of lncRNA-ATB and basic information about the patients were analyzed using the chi-square test. LncRNA-ATB overexpression in human chondrocyte cell line CHON-001 (ATCC CRL-2846) was established to study the effects on chondrocyte proliferation (using the CCK-8 assay) and viability. Results LncRNA-ATB expression was significantly downregulated in the serum of osteoarthritis patients compared with the healthy controls, meaning this downregulation effectively distinguished osteoarthritis patients from healthy subjects. LncRNA-ATB expression in the serum was not significantly affected by the patients’ gender, age or habits, including smoking and alcohol consumption. LncRNA-ATB overexpression activated Akt signaling, promoted proliferation and increased the viability of the chondrocytes. Conclusion We conclude that downregulation of lncRNA-ATB in serum is a reliable diagnostic marker for osteoarthritis and that this lncRNA participates in the pathogenesis of osteoarthritis by regulating the proliferation and viability of chondrocytes through the activation of Akt signaling. Electronic supplementary material The online version of this article (10.1186/s11658-018-0118-9) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Xiliang Dang
- Second Department of Orthopaedics, Wei Nan Central Hospital, Weinan, 714000 Shanxi Province People's Republic of China
| | - Liping Lian
- Second Department of Orthopaedics, Wei Nan Central Hospital, Weinan, 714000 Shanxi Province People's Republic of China
| | - Dongsheng Wu
- Second Department of Orthopaedics, Wei Nan Central Hospital, Weinan, 714000 Shanxi Province People's Republic of China
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Zhang Y, Li J, Jia S, Wang Y, Kang Y, Zhang W. Down-regulation of lncRNA-ATB inhibits epithelial-mesenchymal transition of breast cancer cells by increasing miR-141-3p expression. Biochem Cell Biol 2018; 97:193-200. [PMID: 30352165 DOI: 10.1139/bcb-2018-0168] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Long noncoding RNA activated by transforming growth factor-beta (lnc-ATB) is abnormally expressed in a number of tumor types. The aim of this study was to investigate the expression of lnc-ATB and miR-141-3p, and to determine whether lnc-ATB can regulate epithelial-mesenchymal transition (EMT) by miR-141-3p in breast cancer. Here, we found that lnc-ATB was highly expressed, whereas there was low expression of miR-141-3p in breast cancer tissues and cells. Knockdown of lnc-ATB in two breast cancer cell lines (MDA-MB-231 and BT549) significantly increased miR-141-3p expression. Down-regulation of lnc-ATB resulted in a morphological change of breast cancer cells from spindle-like to a round shape, and in a remarkable inhibition of cell migration and invasion, which were reversed by miR-141-3p inhibitor. Furthermore, we demonstrated that lnc-ATB knockdown decreased ZEB1, ZEB2, N-cadherin, and vimentin expression, and promoted E-cadherin expression, while miR-141-3p inhibitor could reverse those effects. Moreover, we proved that miR-141-3p directly bound to the 3' untranslated region (UTR) of ZEB1 and ZEB2 and negatively regulated ZEB1 and ZEB2 expression. Taken together, our results show that knockdown of lnc-ATB significantly inhibits the EMT process of breast cancer cells by increasing the expression of miR-141-3p, indicating that lnc-ATB might serve as a novel therapeutic target for breast cancer.
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Affiliation(s)
- Yang Zhang
- a Department of the 7th General Surgery and 1st Breast Surgery, Shengjing Hospital of China Medical University, Shenyang 110022, People's Republic of China
| | - Jianyi Li
- a Department of the 7th General Surgery and 1st Breast Surgery, Shengjing Hospital of China Medical University, Shenyang 110022, People's Republic of China
| | - Shi Jia
- a Department of the 7th General Surgery and 1st Breast Surgery, Shengjing Hospital of China Medical University, Shenyang 110022, People's Republic of China
| | - Yitong Wang
- a Department of the 7th General Surgery and 1st Breast Surgery, Shengjing Hospital of China Medical University, Shenyang 110022, People's Republic of China
| | - Ye Kang
- b Department of Pathology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China
| | - Wenhai Zhang
- a Department of the 7th General Surgery and 1st Breast Surgery, Shengjing Hospital of China Medical University, Shenyang 110022, People's Republic of China
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Li ZY, Sun XY. Molecular targets regulating invasion and metastasis of pancreatic cancer. Shijie Huaren Xiaohua Zazhi 2018; 26:1651-1659. [DOI: 10.11569/wcjd.v26.i28.1651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
- Zi-Yi Li
- The Hepatosplenic Surgery Center, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China
| | - Xue-Ying Sun
- The Hepatosplenic Surgery Center, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China
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Shen X, Piao L, Zhang S, Cui Y, Cui Y, Quan X, Sun H. Long non-coding RNA activated by TGF-β expression in cancer prognosis: A meta-analysis. Int J Surg 2018; 58:37-45. [PMID: 30121307 DOI: 10.1016/j.ijsu.2018.08.004] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Revised: 07/22/2018] [Accepted: 08/06/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Recently, long non-coding RNA activated by transforming growth factor beta (TGF-β) (lncRNA ATB) was shown to be useful in cancer prognosis, however, its prognostic value in human cancer has been inconsistent. Our study aimed to explore the prognostic role of lncRNA ATB expression in cancer prognosis. METHODS PubMed, Embase, and Cochrane Library databases were thoroughly searched to retrieve studies focusing on the prognostic role of lncRNA ATB expression in cancer, and meta-analysis was performed. RESULTS A total of 15 studies were included into this meta-analysis. High lncRNA ATB expression was significantly related to shorter overall survival (OS) (HR = 2.44, 95%CI = 1.98-3.01, P < 0.01), recurrence-free survival (RFS) (HR = 1.85, 95%CI = 1.42-2.40, P < 0.01), disease-free survival (DFS) (HR = 3.61, 95%CI = 2.45-5.33, P < 0.01), and progression-free survival (PFS) (HR = 2.97, 95%CI = 2.12-4.16, P < 0.01) when compared with low lncRNA ATB expression in cancer. Moreover, Patients with high lncRNA ATB expression tended to have worse tumor differentiation (P < 0.01), more advanced clinical stage (P < 0.01), deeper tumor invasion (P < 0.01), earlier distant metastases (P = 0.02), lymph node metastases (P = 0.04), and vascular invasion (P < 0.01) when compared with those with low lncRNA ATB expression. CONCLUSIONS High lncRNA ATB expression was significantly associated with worse prognosis in cancer. LncRNA ATB expression could be used as a prognostic biomarker for human cancer.
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Affiliation(s)
- Xionghu Shen
- Department of Oncology, Affiliated Hospital of Yanbian University, Yanji, 133000, Jilin Province, China
| | - Longzhen Piao
- Department of Oncology, Affiliated Hospital of Yanbian University, Yanji, 133000, Jilin Province, China
| | - Songnan Zhang
- Department of Oncology, Affiliated Hospital of Yanbian University, Yanji, 133000, Jilin Province, China
| | - Yan Cui
- Department of Oncology, Affiliated Hospital of Yanbian University, Yanji, 133000, Jilin Province, China
| | - Yuzhen Cui
- Department of Oncology, Affiliated Hospital of Yanbian University, Yanji, 133000, Jilin Province, China
| | - Xianglan Quan
- Department of Oncology, Affiliated Hospital of Yanbian University, Yanji, 133000, Jilin Province, China
| | - Honghua Sun
- Department of Oncology, Affiliated Hospital of Yanbian University, Yanji, 133000, Jilin Province, China.
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Arriaga-Canon C, De La Rosa-Velázquez IA, González-Barrios R, Montiel-Manríquez R, Oliva-Rico D, Jiménez-Trejo F, Cortés-González C, Herrera LA. The use of long non-coding RNAs as prognostic biomarkers and therapeutic targets in prostate cancer. Oncotarget 2018; 9:20872-20890. [PMID: 29755696 PMCID: PMC5945524 DOI: 10.18632/oncotarget.25038] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2017] [Accepted: 03/15/2018] [Indexed: 12/16/2022] Open
Abstract
Prostate cancer is the most common cancer in men and the second leading cause of cancer-related deaths. The most used biomarker to detect prostate cancer is Prostate Specific Antigen (PSA), whose levels are measured in serum. However, it has been recently established that molecular markers of cancer should not be based solely on genes and proteins but should also reflect other genomic traits; long non-coding RNAs (lncRNAs) serve this purpose. lncRNAs are transcripts of >200 bases that do not encode proteins and that have been shown to display abnormal expression profiles in different types of cancer. Experimental studies have highlighted lncRNAs as potential biomarkers for prognoses and treatments in patients with different types of cancer, including prostate cancer, where the PCA3 lncRNA is currently used as a diagnostic tool and management strategy. With the development of genomic technologies, particularly next-generation sequencing (NGS), several other lncRNAs have been linked to prostate cancer and are currently under validation for their medical use. In this review, we will discuss different strategies for the discovery of novel lncRNAs that can be evaluated as prognostic biomarkers, the clinical impact of these lncRNAs and how lncRNAs can be used as potential therapeutic targets.
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Affiliation(s)
| | - Inti Alberto De La Rosa-Velázquez
- Universidad Nacional Autónoma de México, Laboratorio de Genómica, CIC-Red de Apoyo a la Investigación, INCMNSZ, Colonia Belisario Domínguez Sección XVI, Delegación Tlalpan C.P.14080, CDMX, Mexico
| | - Rodrigo González-Barrios
- Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, Tlalpan. C.P. 14080, CDMX, Mexico
| | - Rogelio Montiel-Manríquez
- Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, Tlalpan. C.P. 14080, CDMX, Mexico
| | - Diego Oliva-Rico
- Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, Tlalpan. C.P. 14080, CDMX, Mexico
| | | | - Carlo Cortés-González
- Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, Tlalpan. C.P. 14080, CDMX, Mexico
| | - Luis A Herrera
- Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, Tlalpan. C.P. 14080, CDMX, Mexico
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Sun Z, Zhang B, Cui T. Long non-coding RNA XIST exerts oncogenic functions in pancreatic cancer via miR-34a-5p. Oncol Rep 2018; 39:1591-1600. [PMID: 29393501 PMCID: PMC5868395 DOI: 10.3892/or.2018.6245] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2017] [Accepted: 12/29/2017] [Indexed: 12/11/2022] Open
Abstract
Long non-coding RNAs (lncRNAs) have been implicated in the occurrence and progression of multiple cancers. In the present study, we investigated the role of lncRNA X inactive-specific transcript (XIST) in the development and progression of pancreatic cancer (PC). Firstly, we found that lncRNA XIST was markedly upregulated in PC tissues and PC cell lines, respectively. Overexpression of XIST significantly promoted the proliferation, migration and invasion, and suppressed cell apoptosis of BxPC-3 cells; knockdown of XIST significantly inhibited the proliferation, migration and invasion, and accelerated cell apoptosis of PANC-1 cells. Furthermore, BxPC-3 and PANC-1 cells transfected with different vectors were injected subcutaneously into nude mice to explore tumor formation. We found that XIST promoted tumor formation in vivo. Subsequently, we found that microRNA-34a-5p (miR‑34a-5p) was downregulated in PC tissues, and predicted a poor prognosis in PC patients. In addition, the results indicated that miR-34a-5p is a target gene of XIST and was significantly negatively correlated with XIST. More importantly, we found that miR-34a-5p rescued the facilitation of malignant behavior mediated by XIST. These results indicated that XIST and miR-34a-5p may be potential effective therapeutic targets for PC.
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Affiliation(s)
- Zhixia Sun
- Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130031, P.R. China
| | - Baogang Zhang
- Department of Endoscopy, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130031, P.R. China
| | - Tingting Cui
- Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130031, P.R. China
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Nourbakhsh N, Emadi-Baygi M, Salehi R, Nikpour P. Gene Expression Analysis of Two Epithelial-mesenchymal Transition-related Genes: Long Noncoding RNA-ATB and SETD8 in Gastric Cancer Tissues. Adv Biomed Res 2018; 7:42. [PMID: 29657927 PMCID: PMC5887690 DOI: 10.4103/abr.abr_252_16] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Background Cancer is the second cause of death after cardiovascular diseases worldwide. Tumor metastasis is the main cause of death in patients with cancer; therefore, unraveling the molecular mechanisms involved in metastasis is critical. Epithelial-mesenchymal transition (EMT) is believed to promote tumor metastasis. Based on the critical roles of long noncoding RNA-ATB (lncRNA-ATB) and SETD8 genes in cancer pathogenesis and EMT, in this study, we aimed to assess expression profile and clinicopathological relevance of these two genes in human gastric cancer. Materials and Methods Quantitative real-time polymerase chain reaction was performed to assess these gene expressions in gastric cancer tissues and various cell lines. The associations between these gene expressions and clinicopathological characteristics were also analyzed. Results Insignificant downregulation of lncRNA-ATB and significant upregulation of SETD8 in cancerous versus noncancerous gastric tissues were observed. Among different examined cell lines, all displayed both genes expression. Except for a significant inverse correlation between the expression levels of lncRNA-ATB and depth of invasion (T) and a direct association between SETD8 levels and advanced tumor grades, no significant association was found with other clinicopathological characteristics. Conclusion lncRNA-ATB and SETD8 genes may play a critical role in gastric cancer progression and may serve as potential diagnostic/prognostic biomarkers in cancer patients.
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Affiliation(s)
- Nooshin Nourbakhsh
- Applied Physiology Research Center, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.,Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Modjtaba Emadi-Baygi
- Department of Genetics, Faculty of Basic Sciences, Shahrekord University, Shahrekord, Iran.,Research Institute of Biotechnology, Shahrekord University, Shahrekord, Iran
| | - Rasoul Salehi
- Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Parvaneh Nikpour
- Applied Physiology Research Center, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.,Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.,Child Growth and Development Research Center, Research Institute for Primordial Prevention of Noncommunicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
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Lou Y, Jiang H, Cui Z, Wang X, Wang L, Han Y. Gene microarray analysis of lncRNA and mRNA expression profiles in patients with high‑grade ovarian serous cancer. Int J Mol Med 2018; 42:91-104. [PMID: 29577163 PMCID: PMC5979786 DOI: 10.3892/ijmm.2018.3588] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2017] [Accepted: 03/16/2018] [Indexed: 12/15/2022] Open
Abstract
High-grade ovarian serous cancer is known for its high rates of invasion and metastasis, and resultant high mortality rate. Therefore, research concerning biomarkers and underlying molecular mechanisms of high-grade ovarian serous cancer progression and prognosis are urgently required. Long non-coding RNAs (lncRNAs) have been the subject of an increasing number of studies, and certain lncRNAs have been demonstrated to serve an important function in the development and progression of various cancers, including HOX transcript antisense RNA, competing endogenous lncRNA 2 for microRNA let-7b, urothelial cancer associated 1, and H19, imprinted maternally expressed transcript (non-protein coding). However, few studies have investigated the differential expression of lncRNAs in high-grade ovarian serous cancer. In the present study, differences in lncRNA and mRNA expression profiles between high-grade ovarian serous cancer tissue samples and healthy fallopian tube tissue samples were investigated using microarray analysis, and the differential expression of lncRNAs and mRNAs was confirmed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Then, five abnormally expressed lncRNAs were selected, and the associations between these lncRNAs and ovarian cancer clinicopathological parameters were examined using RT-qPCR. The expression profiles of certain lncRNAs and mRNAs were confirmed to be altered between high-grade ovarian serous cancer tissues and healthy fallopian tube tissues. Furthermore, the expression levels of selected lncRNAs were associated with International Federation of Gynecology and Obstetrics stage and lymph node metastasis. These lncRNAs and mRNAs may therefore be involved in the pathogenesis of high-grade ovarian serous cancer. The results of the present study provide an experimental foundation for further exploration of the value of these lncRNAs and mRNAs in the early diagnosis and treatment of high-grade ovarian serous cancer.
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Affiliation(s)
- Yanhui Lou
- Department of Gynecology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266100, P.R. China
| | - Huanhuan Jiang
- Department of Gynecology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266100, P.R. China
| | - Zhumei Cui
- Department of Gynecology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266100, P.R. China
| | - Xiangyu Wang
- Department of Gynecology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266100, P.R. China
| | - Lingzhi Wang
- Department of Gynecology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266100, P.R. China
| | - Yi Han
- Department of Gynecology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266100, P.R. China
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Hu H, Wang Y, Ding X, He Y, Lu Z, Wu P, Tian L, Yuan H, Liu D, Shi G, Xia T, Yin J, Cai B, Miao Y, Jiang K. Long non-coding RNA XLOC_000647 suppresses progression of pancreatic cancer and decreases epithelial-mesenchymal transition-induced cell invasion by down-regulating NLRP3. Mol Cancer 2018; 17:18. [PMID: 29386037 PMCID: PMC5793431 DOI: 10.1186/s12943-018-0761-9] [Citation(s) in RCA: 63] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2017] [Accepted: 01/05/2018] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Long non-coding RNAs (lncRNAs) play an important role in the development and progression of various tumors, including pancreatic cancer (PC). Recent studies have shown that lncRNAs can 'act in cis' to regulate the expression of its neighboring genes. Previously, we used lncRNAs microarray to identify a novel lncRNA termed XLOC_000647 that was down-regulated in PC tissues. However, the expression and function of XLOC_000647 in PC remain unclear. METHODS The expression of XLOC_000647 and NLRP3 in PC specimens and cell lines were detected by quantitative real-time PCR. Transwell assays were used to determine migration and invasion of PC cells. Western blot was carried out for detection of epithelial-mesenchymal transition (EMT) markers in PC cells. The effect of XLOC_000647 on PC cells was assessed in vitro and in vivo. The function of NOD-like receptor family pyrin domain-containing 3 (NLRP3) in PC was investigated in vitro. In addition, the regulation of NLRP3 by XLOC_000647 in PC was examined in vitro. RESULTS Here, XLOC_000647 expression was down-regulated in PC tissues and cell lines. The expression level of XLOC_000647 was significantly correlated to tumor stage, lymph node metastasis, and overall survival. Overexpression of XLOC_000647 attenuated cell proliferation, invasion, and EMT in vitro and impaired tumor growth in vivo. Further, a significantly negative correlation was observed between XLOC_000647 levels and its genomic nearby gene NLRP3 in vitro and in vivo. Moreover, XLOC_000647 decreased NLRP3 by inhibiting its promoter activity. Knockdown of NLRP3 decreased proliferation of cancer cells, invasion, and EMT in vitro. Importantly, after XLOC_000647 was overexpressed, the corresponding phenotypes of cells invasion and EMT were reversed by overexpression of NLRP3. CONCLUSIONS Together, these results indicate that XLOC_000647 functions as a novel tumor suppressor of lncRNA and acts as an important regulator of NLRP3, inhibiting cell proliferation, invasion, and EMT in PC.
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Affiliation(s)
- Hao Hu
- Pancreas Center, Nanjing Medical University, 300 Guangzhou Rd, Gulou District, Nanjing, Jiangsu Province, 210029, China.,Department of Hepatopancreatobiliary Center, The Third Hospital Affiliated to Nantong University, Wuxi, 214041, China
| | - Yandong Wang
- Pancreas Center, Nanjing Medical University, 300 Guangzhou Rd, Gulou District, Nanjing, Jiangsu Province, 210029, China.,Department of General Surgery, The Second People's Hospital of Wuhu, Wuhu, 241000, China
| | - Xiangya Ding
- Department of Microbiology, Nanjing Medical University, Nanjing, 211166, China
| | - Yuan He
- Pancreas Center, Nanjing Medical University, 300 Guangzhou Rd, Gulou District, Nanjing, Jiangsu Province, 210029, China.,Department of General Surgery, Huai'an Hospital Affiliated to Xuzhou Medical University, Huai'an, 223001, China
| | - Zipeng Lu
- Pancreas Center, Nanjing Medical University, 300 Guangzhou Rd, Gulou District, Nanjing, Jiangsu Province, 210029, China.,Pancreas Institute, Nanjing Medical University, Nanjing, 210029, China
| | - Pengfei Wu
- Pancreas Center, Nanjing Medical University, 300 Guangzhou Rd, Gulou District, Nanjing, Jiangsu Province, 210029, China.,Pancreas Institute, Nanjing Medical University, Nanjing, 210029, China
| | - Lei Tian
- Pancreas Center, Nanjing Medical University, 300 Guangzhou Rd, Gulou District, Nanjing, Jiangsu Province, 210029, China.,Pancreas Institute, Nanjing Medical University, Nanjing, 210029, China
| | - Hao Yuan
- Pancreas Center, Nanjing Medical University, 300 Guangzhou Rd, Gulou District, Nanjing, Jiangsu Province, 210029, China.,Pancreas Institute, Nanjing Medical University, Nanjing, 210029, China
| | - Dongfang Liu
- Pancreas Center, Nanjing Medical University, 300 Guangzhou Rd, Gulou District, Nanjing, Jiangsu Province, 210029, China.,Pancreas Institute, Nanjing Medical University, Nanjing, 210029, China
| | - Guodong Shi
- Pancreas Center, Nanjing Medical University, 300 Guangzhou Rd, Gulou District, Nanjing, Jiangsu Province, 210029, China.,Pancreas Institute, Nanjing Medical University, Nanjing, 210029, China
| | - Tianfang Xia
- Pancreas Center, Nanjing Medical University, 300 Guangzhou Rd, Gulou District, Nanjing, Jiangsu Province, 210029, China.,Department of General Surgery, Huai'an First Hospital Affiliated to Nanjing Medical University, Huai'an, 223001, China
| | - Jie Yin
- Pancreas Center, Nanjing Medical University, 300 Guangzhou Rd, Gulou District, Nanjing, Jiangsu Province, 210029, China.,Pancreas Institute, Nanjing Medical University, Nanjing, 210029, China
| | - Baobao Cai
- Pancreas Center, Nanjing Medical University, 300 Guangzhou Rd, Gulou District, Nanjing, Jiangsu Province, 210029, China.,Pancreas Institute, Nanjing Medical University, Nanjing, 210029, China
| | - Yi Miao
- Pancreas Center, Nanjing Medical University, 300 Guangzhou Rd, Gulou District, Nanjing, Jiangsu Province, 210029, China. .,Pancreas Institute, Nanjing Medical University, Nanjing, 210029, China.
| | - Kuirong Jiang
- Pancreas Center, Nanjing Medical University, 300 Guangzhou Rd, Gulou District, Nanjing, Jiangsu Province, 210029, China. .,Pancreas Institute, Nanjing Medical University, Nanjing, 210029, China.
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Xiao H, Zhang F, Zou Y, Li J, Liu Y, Huang W. The Function and Mechanism of Long Non-coding RNA-ATB in Cancers. Front Physiol 2018; 9:321. [PMID: 29692736 PMCID: PMC5902489 DOI: 10.3389/fphys.2018.00321] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2017] [Accepted: 03/15/2018] [Indexed: 02/05/2023] Open
Abstract
Long non-coding RNAs (lncRNAs) are a class of transcriptional RNA molecules with a length of greater than 200 nucleotides that function as regulatory factors in many human diseases. Studies have shown that lncRNAs are involved in multiple cellular processes, including proliferation, apoptosis, migration, and invasion. In this report, a long non-coding RNA-ATB that is overexpressed in various tumor tissues and cell lines was investigated. Recent evidence suggests that ATB is dysfunctional in a variety of cancers, including hepatocellular carcinoma, gastric cancer (GC), colorectal cancer (CRC), breast cancer (BC), prostate cancer, renal cell carcinoma, non-small cell lung cancer (NSCLC), pancreatic cancer, osteosarcoma, and glioma. The high expression of ATB is associated with clinicopathological features of cancer patients. In addition, overexpression of lncRNA-ATB can promote tumor proliferation, migration, and invasion. LncRNA-ATB induces epithelial-mesenchymal transition (EMT) by competitively binding to miRNAs, thus promoting tumor progression. Biological functions and mechanisms of ATB in human cancers are discussed here, concluding that lncRNA-ATB may provide a new biomarker for use in diagnosis and prognosis of cancer.
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Affiliation(s)
- Huizhong Xiao
- Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, China
- University of South China, Hengyang, China
| | - Fuyou Zhang
- Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, China
| | - Yifan Zou
- Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, China
- Shantou University Medical College, Shantou, China
| | - Jianfa Li
- Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, China
- Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen, PKU-HKUST Medical Center, Shenzhen, China
| | - Yuchen Liu
- Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, China
- *Correspondence: Yuchen Liu
| | - Weiren Huang
- Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, China
- University of South China, Hengyang, China
- Shantou University Medical College, Shantou, China
- Weiren Huang
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39
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Chen Y, Wei G, Xia H, Tang Q, Bi F. Long noncoding RNA‑ATB promotes cell proliferation, migration and invasion in gastric cancer. Mol Med Rep 2017; 17:1940-1946. [PMID: 29257203 DOI: 10.3892/mmr.2017.8077] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2016] [Accepted: 08/08/2017] [Indexed: 02/05/2023] Open
Abstract
Long noncoding RNA (lncRNA)‑activated by transforming growth factor (TGF)-β (lncRNA-ATB) was recognized as an unfavorable prognostic factor in various cancers; however, its regulatory role in gastric cancer (GC) remains elusive. The present study aimed to measure lncRNA‑ATB expression in GC and to explore its involvement in GC progression. lncRNA‑ATB expression levels were measured in 40 pairs of GC tissues and their normal adjacent tissues, as well as in 5 GC cell lines and a normal gastric mucosal cell line by reverse transcription-quantitative polymerase chain reaction. Knockdown experiments were performed to explore the effect of lncRNA‑ATB on the cell proliferation, invasion and migration. The results demonstrated that lncRNA‑ATB expression levels in GC tissues and GC cell lines were significantly higher than in the adjacent normal tissues and normal gastric mucosal cells. Further analysis of the correlation between the clinicopathological features and lncRNA‑ATB expression indicated that higher expression of lncRNA‑ATB was correlated with increased invasion depth, more distant metastasis and advanced tumor‑node‑metastasis stage. In addition, downregulated lncRNA‑ATB expression suppressed cellular proliferation, invasion and migration of GC cells. In conclusion, these data suggested that lncRNA‑ATB may serve as a clinical outcome predictor and potential therapeutic target in GC.
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Affiliation(s)
- Ying Chen
- Department of Medical Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Guoqing Wei
- Laboratory of Signal Transduction and Molecular Targeted Therapy, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Hongwei Xia
- Laboratory of Signal Transduction and Molecular Targeted Therapy, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Qiulin Tang
- Laboratory of Signal Transduction and Molecular Targeted Therapy, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Feng Bi
- Department of Medical Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
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40
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Jang SY, Kim G, Park SY, Lee YR, Kwon SH, Kim HS, Yoon JS, Lee JS, Kweon YO, Ha HT, Chun JM, Han YS, Lee WK, Chang JY, Park JG, Lee B, Tak WY, Hur K. Clinical significance of lncRNA-ATB expression in human hepatocellular carcinoma. Oncotarget 2017; 8:78588-78597. [PMID: 29108251 PMCID: PMC5667984 DOI: 10.18632/oncotarget.21094] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2017] [Accepted: 09/04/2017] [Indexed: 01/14/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a worldwide health problem and it is important to understand the mechanistic roles of the biomolecules involved in its pathogenesis. Long non-coding RNAs (lncRNAs) are frequently and aberrantly expressed in various human cancers and are known to play a role in cancer pathogenesis. The aim of this study was to analyze the expression of lncRNA-ATB in HCC and investigate the implications for prognoses. In total, 100 samples of HCC tissues and their corresponding, adjacent, non-cancerous liver tissues were collected. Total RNAs were extracted and the expression levels of lncRNA-ATB were measured by qRT-PCR. The association of lncRNA expression with clinicopathological features and patient survival were then analyzed. LncRNA-ATB was significantly upregulated in HCC tissues compared with the levels in corresponding non-cancerous tissues. Expression of lncRNA-ATB was significantly associated with portal vein thrombosis, intrahepatic or extrahepatic metastases, mUICC stage, and the BCLC stage. Large tumors (> 5 cm, HR = 3.851, 95% CI = 1.431–10.364, p = 0.008) and higher lncRNA-ATB expression (HR = 4.158, 95% CI = 1.226–14.107, p = 0.022) were the significant prognostic factors for overall survival. With this novel evidence of the involvement of lncRNA-ATB in HCC pathogenesis and clinical features, lncRNA-ATB can be concluded to have potential as a biomarker for the prognosis of HCC and as a targeted therapy for afflicted patients.
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Affiliation(s)
- Se Young Jang
- Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea
| | - Gyeonghwa Kim
- Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Soo Young Park
- Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea
| | - Yu Rim Lee
- Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea
| | - Sang Hoon Kwon
- Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea
| | - Hyeong Seok Kim
- Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea
| | - Jun Sik Yoon
- Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea
| | - Jun Seob Lee
- Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea
| | - Young-Oh Kweon
- Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea
| | - Heon Tak Ha
- Department of Surgery, Kyungpook National University School of Medicine, Daegu, Republic of Korea
| | - Jae Min Chun
- Department of Surgery, Kyungpook National University School of Medicine, Daegu, Republic of Korea
| | - Young Seok Han
- Department of Surgery, Kyungpook National University School of Medicine, Daegu, Republic of Korea
| | - Won Kee Lee
- Biostatistics, Medical Research Collaboration Center in Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Republic of Korea
| | - Jun Young Chang
- Department of Neurology, Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea
| | - Jung Gil Park
- Department of Internal Medicine, College of Medicine, Yeungnam University, Daegu, Republic of Korea
| | - Byungheon Lee
- Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Won Young Tak
- Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea
| | - Keun Hur
- Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
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41
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Li J, Li Z, Zheng W, Li X, Wang Z, Cui Y, Jiang X. LncRNA-ATB: An indispensable cancer-related long noncoding RNA. Cell Prolif 2017; 50. [PMID: 28884871 DOI: 10.1111/cpr.12381] [Citation(s) in RCA: 141] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2017] [Accepted: 08/06/2017] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVES Long non-coding RNAs (lncRNAs) are a group of non-protein-coding RNAs that are greater than 200 nucleotides in length. Increasing evidence indicates that lncRNAs, which may serve as either oncogenes or tumour suppressor genes, play a vital role in the pathophysiology of human diseases, especially in tumourigenesis and progression. Deregulation of lncRNAs impacts different cellular processes, such as proliferation, dedifferentiation, migration, invasion and anti-apoptosis. The aim of this review was to explore the molecular mechanism and clinical significance of long non-coding RNA-activated by transforming growth factor β (lncRNA-ATB) in various types of cancers. MATERIALS AND METHODS In this review, we summarize and analyze current studies concerning the biological functions and mechanisms of lncRNA-ATB in tumour development. The related studies were obtained through a systematic search of Pubmed, Web of Science, Embase and Cochrane Library. RESULTS Long non-coding RNAs-ATB is a novel cancer-related lncRNA that was recently found to exhibit aberrant expression in a variety of malignancies, including hepatocellular carcinoma, colorectal cancer, gastric cancer, and lung cancer. Dysregulation of lncRNA-ATB has been shown to contribute to proliferation, migration and invasion of cancer cells. Long non-coding RNAs-ATB promotes tumourigenesis and progression mainly through competitively binding miRNAs to induce epithelial-mesenchymal transition (EMT). CONCLUSIONS Long non-coding RNAs-ATB likely represents a feasible cancer biomarker or therapeutic target.
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Affiliation(s)
- Jinglin Li
- Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Zhenglong Li
- Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Wangyang Zheng
- Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xinheng Li
- Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Zhidong Wang
- Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Yunfu Cui
- Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xingming Jiang
- Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China
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Huang X, Ta N, Zhang Y, Gao Y, Hu R, Deng L, Zhang B, Jiang H, Zheng J. Microarray Analysis of the Expression Profile of Long Non-Coding RNAs Indicates lncRNA RP11-263F15.1 as a Biomarker for Diagnosis and Prognostic Prediction of Pancreatic Ductal Adenocarcinoma. J Cancer 2017; 8:2740-2755. [PMID: 28928863 PMCID: PMC5604206 DOI: 10.7150/jca.18073] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2016] [Accepted: 03/16/2017] [Indexed: 02/07/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignancy with poor prognostic outcomes. Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) play an important role in the development and progression of carcinogenesis. Nevertheless, little is known about the role of lncRNAs in PDAC. The aim of the current study was to find differentially expressed lncRNAs and related mRNAs in human PDAC tissues and adjacent normal tissues by microarray analysis, and investigate the relationship between lncRNA RP11-263F15.1 levels and the clinicaopathological features of PDAC patients. It was found that 4364 lncRNAs and 4862 related mRNAs were significantly dysregulated in PDAC tissues as compared with adjacent normal tissues with a fold change ≥2.0 (P<0.05). GO and pathway analyses showed that the up-regulated gene profiles were related to several pathways associated with carcinogenesis, while the down-regulated gene profiles were closely correlated with nutrient metabolism. RP11-263F15.1 levels were associated with histologic differentiation (P=0.001). Besides, Kaplan-Meier analysis showed that high expression of RP11-263F15.1 was associated with poor outcomes, but multivariate analysis suggested that RP11-263F15.1 was not an independent factor for predicting prognosis of PDAC. In conclusion, these data indicate that differentially expressed lncRNAs and mRNAs were involved in the carcinogenesis of PDAC, and RP11-263F15.1 may prove to be a potential biomarker for the diagnosis and prognostic prediction of PDAC.
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Affiliation(s)
- Xiaoyi Huang
- Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
| | - Na Ta
- Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
| | - Yunshuo Zhang
- Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
| | - Yisha Gao
- Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
| | - Ronglei Hu
- Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
| | - Lulu Deng
- Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
| | - Bingbing Zhang
- Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
| | - Hui Jiang
- Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
| | - Jianming Zheng
- Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
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43
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Zheng C, Hao H, Chen L, Shao J. Long noncoding RNAs as novel serum biomarkers for the diagnosis of hepatocellular carcinoma: a systematic review and meta-analysis. Clin Transl Oncol 2017; 19:961-968. [PMID: 28188488 DOI: 10.1007/s12094-017-1626-1] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2016] [Accepted: 01/28/2017] [Indexed: 12/16/2022]
Abstract
PURPOSE Long noncoding RNAs (lncRNAs) are outstanding as novel cancer biomarkers with great prospects. Herein, we focused on summarizing the overall diagnostic evaluation of lncRNAs for hepatocellular carcinoma (HCC). METHODS Relevant literature was collected from the online databases. The Quality Assessment for Studies of Diagnostic Accuracy checklist was used to assess the quality of included studies. The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were plotted using random-effects models. Summary receiver operating characteristic curve and the area under the curve (AUC) were used to estimate the overall test performance. Statistical analysis was performed by STATA 14.0 and Meta-DiSc 1.4 software. RESULTS Ten studies with a total of 820 HCC patients and 785 healthy controls were included. For overall lncRNAs, the pooled sensitivity, specificity, and DOR to predict HCC patients were 80% [95% confidence interval (CI) 77-82%], 79% (95% CI 76-81%), and 27.66 (95% CI 14.26-53.63), respectively, corresponding to an AUC of 0.91. CONCLUSIONS LncRNAs were a high diagnostic value for HCC and its expression could potentially be used as auxiliary biomarker in confirming HCC.
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Affiliation(s)
- C Zheng
- Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, 330000, China
- Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, 330000, China
| | - H Hao
- Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, 330000, China
- Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, 330000, China
| | - L Chen
- Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, 330000, China
- Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, 330000, China
| | - J Shao
- Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, 330000, China.
- Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, 330000, China.
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44
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Han M, Xu W. EMP3 is induced by TWIST1/2 and regulates epithelial-to-mesenchymal transition of gastric cancer cells. Tumour Biol 2017; 39:1010428317718404. [PMID: 28718375 DOI: 10.1177/1010428317718404] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
In this study, we aimed to explore new downstream effectors of TWIST1/2 in inducing epithelial-to-mesenchymal transition in gastric cancer. Bioinformatic data mining was performed using data in The Cancer Genome Atlas Stomach Adenocarcinoma. Survival curves were generated using Kaplan-Meier plotter. Gastric cancer cell lines (AGS and SGC-7901) were used as in vitro cell model to investigate the regulative effect of TWIST1/2 on epithelial membrane protein 3 expression and the progression of epithelial-to-mesenchymal transition. Results showed that TWIST1 and TWIST2 are usually co-upregulated in patients with primary gastric cancer. High TWIST1 expression is associated with worse overall survival (hazard ratio = 1.26; 95% confidence interval = 1.06-1.49; p = 0.007) and also worse first progression-free survival (hazard ratio = 1.47; 95% confidence interval = 1.18-1.82; p < 0.0001). Similarly, high TWIST2 expression is associated with unfavorable overall survival (hazard ratio = 1.71; 95% confidence interval = 1.32-2.22; p < 0.0001) and progression-free survival (hazard ratio = 1.99; 95% confidence interval = 1.45-2.72; p < 0.0001). Epithelial membrane protein 3 is negatively correlated to CDH1 expression (Pearson's r = -0.46) but is positively correlated to VIM expression (Pearson's r = 0.83). Knockdown of epithelial membrane protein 3 significantly increased E-cadherin but significantly decreased Vimentin expression in AGS cells. Gastric cancer patients with metastasis have significantly higher epithelial membrane protein 3 expression than the cases without metastasis. In addition, high epithelial membrane protein 3 expression is associated with worse overall survival (hazard ratio = 2.59; 95% confidence interval = 2.06-3.26; p < 0.0001) and also worse progression-free survival (hazard ratio = 2.21; 95% confidence interval = 1.78-2.74; p < 0.0001). In conclusion, epithelial membrane protein 3 is a downstream effector of TWIST1/2 in inducing epithelial-to-mesenchymal transition in gastric cancer. Epithelial membrane protein 3 upregulation might be associated with gastric cancer metastasis and is a potential indicator of unfavorable overall survival and progression-free survival in gastric cancer patients.
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Affiliation(s)
- Ming Han
- 1 School of Clinical Medicine, Weifang Medical University, Weifang, China
| | - Wanpeng Xu
- 2 Department of Gastrointestinal and Anal Diseases Surgery, Affiliated Hospital of Weifang Medical University, Weifang, China
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Li Z, Wu X, Gu L, Shen Q, Luo W, Deng C, Zhou Q, Chen X, Li Y, Lim Z, Wang X, Wang J, Yang X. Long non-coding RNA ATB promotes malignancy of esophageal squamous cell carcinoma by regulating miR-200b/Kindlin-2 axis. Cell Death Dis 2017. [PMID: 28640252 PMCID: PMC5520904 DOI: 10.1038/cddis.2017.245] [Citation(s) in RCA: 67] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer-related death, especially in China. In addition, the prognosis of late stage patients is extremely poor. However, the biological significance of the long non-coding RNA lnc-ATB and its potential role in ESCC remain to be documented. In this study, we investigated the role of lnc-ATB and the underlying mechanism promoting its oncogenic activity in ESCC. Expression of lnc-ATB was higher in ESCC tissues and cell lines than that in normal counterparts. Upregulated lnc-ATB served as an independent prognosis predictor of ESCC patients. Moreover, loss-of-function assays in ESCC cells showed that knockdown of lnc-ATB inhibited cell proliferation and migration both in vitro and in vivo. Mechanistic investigation indicated that lnc-ATB exerted oncogenic activities via regulating Kindlin-2, as the anti-migration role of lnc-ATB silence was attenuated by ectopic expression of Kindlin-2. Further analysis showed that lnc-ATB functions as a molecular sponge for miR-200b and Kindlin-2. Dysregulated miR-200b/Kindlin-2 signaling mediated the oncogenic activity of lnc-ATB in ESCC. Our results suggest that lnc-ATB predicts poor prognosis and may serve as a potential therapeutic target for ESCC patients.
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Affiliation(s)
- Zhongwen Li
- Department of Oncology, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Xiaoliang Wu
- Department of Oncology, Guizhou Provincial People's Hospital, Guiyang, China.,State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Ling Gu
- State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Puer University, Puer, China
| | - Qi Shen
- Department of Oncology, Guizhou Provincial People's Hospital, Guiyang, China
| | - Wen Luo
- Department of Oncology, Guizhou Provincial People's Hospital, Guiyang, China
| | - Chuangzhong Deng
- State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Qianghua Zhou
- State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Xinru Chen
- State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Yanjie Li
- The 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - ZuanFu Lim
- WVU Cancer Institute, Mary Babb Randolph Cancer Institute, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, WV, USA
| | - Xing Wang
- State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Jiahong Wang
- State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| | - Xianzi Yang
- State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
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46
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Heery R, Finn SP, Cuffe S, Gray SG. Long Non-Coding RNAs: Key Regulators of Epithelial-Mesenchymal Transition, Tumour Drug Resistance and Cancer Stem Cells. Cancers (Basel) 2017; 9:cancers9040038. [PMID: 28430163 PMCID: PMC5406713 DOI: 10.3390/cancers9040038] [Citation(s) in RCA: 137] [Impact Index Per Article: 17.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2017] [Revised: 04/14/2017] [Accepted: 04/18/2017] [Indexed: 02/07/2023] Open
Abstract
Epithelial mesenchymal transition (EMT), the adoption by epithelial cells of a mesenchymal-like phenotype, is a process co-opted by carcinoma cells in order to initiate invasion and metastasis. In addition, it is becoming clear that is instrumental to both the development of drug resistance by tumour cells and in the generation and maintenance of cancer stem cells. EMT is thus a pivotal process during tumour progression and poses a major barrier to the successful treatment of cancer. Non-coding RNAs (ncRNA) often utilize epigenetic programs to regulate both gene expression and chromatin structure. One type of ncRNA, called long non-coding RNAs (lncRNAs), has become increasingly recognized as being both highly dysregulated in cancer and to play a variety of different roles in tumourigenesis. Indeed, over the last few years, lncRNAs have rapidly emerged as key regulators of EMT in cancer. In this review, we discuss the lncRNAs that have been associated with the EMT process in cancer and the variety of molecular mechanisms and signalling pathways through which they regulate EMT, and finally discuss how these EMT-regulating lncRNAs impact on both anti-cancer drug resistance and the cancer stem cell phenotype.
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Affiliation(s)
- Richard Heery
- Thoracic Oncology Research Group, Rm 2.09, Trinity Translational Medical Institute, St. James's Hospital, Dublin D08 W9RT, Ireland.
- Masters in Translational Oncology Program, Department of Surgery, Trinity College Dublin, Trinity Translational Medical Institute, St. James's Hospital, Dublin D08 W9RT, Ireland.
| | - Stephen P Finn
- Department of Histopathology & Morbid Anatomy, Trinity College Dublin, Dublin D08 RX0X, Ireland.
| | - Sinead Cuffe
- HOPE Directorate, St. James's Hospital, Dublin D08 RT2X, Ireland.
| | - Steven G Gray
- Thoracic Oncology Research Group, Rm 2.09, Trinity Translational Medical Institute, St. James's Hospital, Dublin D08 W9RT, Ireland.
- HOPE Directorate, St. James's Hospital, Dublin D08 RT2X, Ireland.
- Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin D02 R590, Ireland.
- Labmed Directorate, St. James's Hospital, Dublin D08 K0Y5, Ireland.
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47
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Noncoding RNAs in the development, diagnosis, and prognosis of colorectal cancer. Transl Res 2017; 181:108-120. [PMID: 27810413 DOI: 10.1016/j.trsl.2016.10.001] [Citation(s) in RCA: 73] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2016] [Revised: 09/29/2016] [Accepted: 10/06/2016] [Indexed: 12/17/2022]
Abstract
More than 90% of the human genome is actively transcribed, but less than 2% of the total genome encodes protein-coding RNA, and thus, noncoding RNA (ncRNA) is a major component of the human transcriptome. Recently, ncRNA was demonstrated to play important roles in multiple biological processes by directly or indirectly interfering with gene expression, and the dysregulation of ncRNA is associated with a variety of diseases, including cancer. In this review, we summarize the function and mechanism of miRNA, long intergenic ncRNA, and some other types of ncRNAs, such as small nucleolar RNA, circular ncRNA, pseudogene RNA, and even protein-coding mRNA, in the progression of colorectal cancer (CRC). We also presented their clinical application in the diagnosis and prognosis of CRC. The summary of the current state of ncRNA in CRC will contribute to our understanding of the complex processes of CRC initiation and development and will help in the discovery of novel biomarkers and therapeutic targets for CRC diagnosis and treatment.
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48
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Fan YH, Ji CX, Xu B, Fan HY, Cheng ZJ, Zhu XG. Long noncoding RNA activated by TGF-β in human cancers: A meta-analysis. Clin Chim Acta 2017; 468:10-16. [PMID: 28163033 DOI: 10.1016/j.cca.2017.02.001] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2016] [Revised: 01/30/2017] [Accepted: 02/01/2017] [Indexed: 01/10/2023]
Abstract
BACKGROUND Because long non-coding RNA ATB (activated by TGF-β) is dysregulated in many cancers, we performed a meta-analysis to determine its prognostic potential in malignant tumors. METHODS We searched electronic databases, including PubMed, Medline, OVID, Cochrane Library and Web of Science from inception until November 15, 2016 and identified eight studies with 818 cancer patients for the meta-analysis. We analyzed the hazard ratios (HRs) and 95% confidence intervals (CIs) to determine the relationship between lncRNA-ATB expression and overall survival (OS), recurrence -free survival (RFS), disease-free survival (DFS). We also use RevMan5.3 software to calculate odds ratio (ORs) to assess the association between lncRNA-ATB expression and pathological parameters including lymph node metastasis (LNM), distant metastasis (DM) and tumor stage. RESULTS Our analysis showed that increased lncRNA-ATB expression was associated with OS (HR=2.82, 95% CI:1.98-4.00, P<0.00001), DFS (HR=2.75, 95% CI:1.73-4.38, P<0.0001), RFS(HR=3.96, 95% CI:2.30-6.81, P<0.00001), LNM (OR=4.07, 95% CI 1.74-9.53, P=0.001), DM (OR=3.21, 95% CI 1.06-9.72, P=0.04) and high tumor stage (OR=2.81, 95% 1.78-4.43, P<0.0001) in patients with other types of cancers that excluded pancreatic cancer. CONCLUSIONS Meta-analysis demonstrated that increased lncRNA-ATB expression can be a useful prognostic biomarker in human cancer.
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Affiliation(s)
- Yang-Hua Fan
- Department of Neurosurgery, The Second Affiliated Hospital, Nanchang University, Nanchang, China
| | - Chen-Xing Ji
- Department of Neurosurgery, The Second Affiliated Hospital, Nanchang University, Nanchang, China
| | - Bing Xu
- Department of Neurosurgery, The Second Affiliated Hospital, Nanchang University, Nanchang, China
| | - Heng-Yi Fan
- Department of Neurosurgery, The Second Affiliated Hospital, Nanchang University, Nanchang, China
| | - Zu-Jue Cheng
- Department of Neurosurgery, The Second Affiliated Hospital, Nanchang University, Nanchang, China.
| | - Xin-Gen Zhu
- Department of Neurosurgery, The Second Affiliated Hospital, Nanchang University, Nanchang, China.
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Schorn S, Demir IE, Haller B, Scheufele F, Reyes CM, Tieftrunk E, Sargut M, Goess R, Friess H, Ceyhan GO. The influence of neural invasion on survival and tumor recurrence in pancreatic ductal adenocarcinoma - A systematic review and meta-analysis. Surg Oncol 2017; 26:105-115. [PMID: 28317579 DOI: 10.1016/j.suronc.2017.01.007] [Citation(s) in RCA: 99] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2016] [Revised: 01/28/2017] [Accepted: 01/31/2017] [Indexed: 12/18/2022]
Abstract
OBJECTIVES To assess the impact of neural invasion/NI on overall survival/OS and tumor recurrence in pancreatic ductal adenocarcinoma/PDAC. SUMMARY BACKGROUND DATA NI is a histopathological hallmark of PDAC. Although some studies suggested an important role for NI on OS, disease-free/DFS and progression-free survival/PFS in PDAC, there is still no consensus on the actual role of NI on survival and local recurrence in PDAC. METHODS Pubmed, Cochrane library, Ovid and Google Scholar were screened for the terms "pancreatic ductal adenocarcinoma", "pancreatic cancer", "survival", "tumor recurrence" and "perineural invasion". The Preferred-Reporting-Items-for-Systematic-review-and-Meta-Analysis/PRISMA-guidelines were used for systematic review and meta-analysis. Articles meeting predefined criteria were critically analysed on relevance, and meta-analyses were performed by pooling univariate and multivariate hazard ratios/HR. RESULTS A total number of 25 studies on the influence of NI on tumor recurrence, and 121 studies analysing the influence of NI on survival were identified by systematic review. The HR of the univariate (HR 1.88; 95%-CI 1.71-2.07; p < 0.00001) and multivariate meta-analysis (HR 1.68; 95%-CI 1.47-1.92; p < 0.00001) showed a major impact of NI on OS. Likewise, NI was associated with decreased DFS (HR 2.53; 95%-CI: 1.67-3.83; p = 0.0001) and PFS (HR 2.41; 95%-CI: 1.73-3.37: p < 0.00001) multivariate meta-analysis. CONCLUSIONS Although the power of this study is limited by missing pathological procedures to assess the true incidence of NI, NI appears to be an independent prognostic factor for OS, DFS and PFS in PDAC. Therefore, NI should be increasingly considered in patient stratification and in the development of novel therapeutic algorithms.
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Affiliation(s)
- Stephan Schorn
- Department of Surgery, Klinikum Rechts der Isar, Technical University of Munich, Germany
| | - Ihsan Ekin Demir
- Department of Surgery, Klinikum Rechts der Isar, Technical University of Munich, Germany
| | - Bernhard Haller
- Institute of Medical Statistics and Epidemiology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany
| | - Florian Scheufele
- Department of Surgery, Klinikum Rechts der Isar, Technical University of Munich, Germany
| | - Carmen Mota Reyes
- Department of Surgery, Klinikum Rechts der Isar, Technical University of Munich, Germany
| | - Elke Tieftrunk
- Department of Surgery, Klinikum Rechts der Isar, Technical University of Munich, Germany
| | - Mine Sargut
- Department of Surgery, Klinikum Rechts der Isar, Technical University of Munich, Germany
| | - Ruediger Goess
- Department of Surgery, Klinikum Rechts der Isar, Technical University of Munich, Germany
| | - Helmut Friess
- Department of Surgery, Klinikum Rechts der Isar, Technical University of Munich, Germany
| | - Güralp Onur Ceyhan
- Department of Surgery, Klinikum Rechts der Isar, Technical University of Munich, Germany.
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50
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Nikpayam E, Soudyab M, Tasharrofi B, Sarrafzadeh S, Iranpour M, Geranpayeh L, Mirfakhraie R, Gharesouran J, Ghafouri-Fard S. Expression analysis of long non-coding ATB and its putative target in breast cancer. Breast Dis 2017; 37:11-20. [PMID: 28598827 DOI: 10.3233/bd-160264] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
BACKGROUND A long noncoding RNA (lncRNA) activated by transforming growth factor (TGF)-β (lncRNA-ATB) has been recently shown to promote the invasion-metastasis cascade in various types of cancers via upregulation of some targets including ZEB1. OBJECTIVES The aim of the present study was to elucidate the expression of lncRNA-ATB and ZEB in breast cancer patients. METHODS The expression of these genes was evaluated by real-time reverse transcription polymerase chain reaction in tumor samples form 50 newly diagnosed breast cancer patients as well as their corresponding adjacent non-cancerous tissues (ANCTs). Patients were divided into subsequent groups according to the median lncRNA-ATB expression. RESULTS LncRNA-ATB has been shown to be downregulated in about two third of tumor samples compared with their ANCTs.A significant association has been found between ZEB1 expression and Ki-67 status. In addition, we demonstrated a correlation between expression of lncRNA-ATB and ZEB1 in tumor samples and not in ANCTs. CONCLUSION Collectively, out data show downregulation of lncRNA-ATB in a significant number of breast tumor tissues compared with ANCTs and imply that lncRNA-ATB might have distinct roles in the pathogenesis of different cancers or even different subtypes of a certain cancer which should be evaluated in future studies.
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MESH Headings
- Adult
- Aged
- Aged, 80 and over
- Breast/metabolism
- Breast Neoplasms/genetics
- Breast Neoplasms/metabolism
- Breast Neoplasms/pathology
- Cadherins/metabolism
- Carcinoma, Ductal, Breast/genetics
- Carcinoma, Ductal, Breast/metabolism
- Carcinoma, Ductal, Breast/pathology
- Down-Regulation
- Female
- Gene Expression
- Humans
- Ki-67 Antigen/metabolism
- Middle Aged
- RNA, Long Noncoding/genetics
- Receptor, ErbB-2/metabolism
- Receptors, Estrogen/metabolism
- Receptors, Progesterone/metabolism
- Transforming Growth Factor beta/genetics
- Transforming Growth Factor beta/metabolism
- Young Adult
- Zinc Finger E-box-Binding Homeobox 1/genetics
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Affiliation(s)
- Elahe Nikpayam
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Soudyab
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Behnoosh Tasharrofi
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shaghayegh Sarrafzadeh
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mostafa Iranpour
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Lobat Geranpayeh
- Department of Surgery, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Mirfakhraie
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Jalal Gharesouran
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Soudeh Ghafouri-Fard
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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