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Zhang G, Wang N, Ma S, Zhang Y, Tao P, Cai H. Comprehensive Analysis of Potential Common Pathogenic Mechanisms for COVID-19 Infection and Gastric Cancer. Anal Cell Pathol (Amst) 2025; 2025:5106674. [PMID: 40224213 PMCID: PMC11991771 DOI: 10.1155/ancp/5106674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Revised: 12/16/2024] [Accepted: 01/25/2025] [Indexed: 04/15/2025] Open
Abstract
A growing body of data suggests that the prevalence of COVID-19 pneumonia in patients with stomach cancer is much higher than in the general population. However, these mechanisms are still not fully understood. After a thorough examination of shared differentially expressed genes (DEGs) for gastric cancer (GC) and COVID-19 pneumonia, we performed functional annotation, protein-protein interaction (PPI) networks, module design, and pivot gene identification. qPCR was used to verify the expression of hub genes in GC. Finally, a pivotal gene transcription factor-gene regulatory network was created and validated. According to functional enrichment analysis, common genes are mainly enriched in biological processes such as extracellular matrix tissue and extracellular structural tissue. Finally, five genes were found to be pivotal genes in the pathogenesis of GC and COVID-19 pneumonia: BGN (biglycan), UBE2C (ubiquitin-conjugating enzymes 2C), SPP1 (secreted phosphoprotein 1), THBS2 (thrombospondin 2), and COL1A1 (type I collagen alpha 1). These shared pathways and pivotal genes could provide new insights for more mechanistic studies.
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Affiliation(s)
- Guiqian Zhang
- Otorhinolaryngology Head and Neck Surgery, The 940th Hospital of Joint Logistics Support Force of People's Liberation Army, Lanzhou, China
| | - Ning Wang
- The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, China
| | - Shixun Ma
- Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Lanzhou, China
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou, China
- NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Lanzhou, China
| | - Yan Zhang
- Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Lanzhou, China
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou, China
- NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Lanzhou, China
| | - Pengxian Tao
- Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Lanzhou, China
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou, China
- Cadre Ward of General Surgery Department, Gansu Provincial Hospital, Lanzhou, China
| | - Hui Cai
- Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Lanzhou, China
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou, China
- NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Lanzhou, China
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Sun N, Zhang Z, Yang X, Li J, Li Q, Kang J, Wei Y, Yu X, Du R, Hong X, Liu G, Gao H, Liu D. Unveiling urinary extracellular vesicle mRNA signature for early diagnosis and prognosis of bladder cancer. Theranostics 2025; 15:1272-1284. [PMID: 39816677 PMCID: PMC11729556 DOI: 10.7150/thno.107213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Accepted: 12/07/2024] [Indexed: 01/18/2025] Open
Abstract
Background: Bladder cancer (BC) ranks as one of the most prevalent cancers. Its early diagnosis is clinically essential but remains challenging due to the lack of reliable biomarkers. Extracellular vesicles (EVs) carry abundant biological cargoes from parental cells, rendering them as promising cancer biomarkers. Herein, we revealed that urinary EVs (uEVs) mRNA signature could serve as non-invasive biomarker for the early diagnosis and prognostic assessment for BC. Methods: Transcriptomic sequencing was conducted to reveal the mRNA signature of EVs collected from normal cell line and different grades of BC cell lines. Candidate EV-mRNA biomarkers were further profiled using clinical urine samples (n = 97, including healthy controls, BC patients and post-surgery BC patients) by RT-qPCR. Results: Three mRNAs (SRGN, FLI1, and MACROH2A2) within uEV were identified as potential biomarkers for BC, providing an area under the receiver operating characteristic curve (AUC) of 0.973 for BC diagnosis. Moreover, the uEV-mRNA panel could discriminate early-stage BC patients from healthy controls with an AUC of 0.969. Finally, we found that the uEV-mRNAs were significantly down-regulated in the post-surgery urine samples of BC patients. Conclusions: Given the facile and non-intrusive nature of urine collection, the identified uEV-mRNAs could serve as potential liquid-biopsy biomarkers for the early diagnosis and prognosis of BC.
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Affiliation(s)
- Ning Sun
- State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Molecular Recognition and Biosensing, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China
| | - Zhaowei Zhang
- State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Molecular Recognition and Biosensing, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China
| | - Xiaoqing Yang
- Tianjin Institute of Urology, the Second Hospital of Tianjin Medical University, Tianjin 300211, China
| | - Jingqi Li
- State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Molecular Recognition and Biosensing, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China
| | - Qiang Li
- State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Molecular Recognition and Biosensing, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China
| | - Jingjing Kang
- State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Molecular Recognition and Biosensing, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China
| | - Yongchun Wei
- State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Molecular Recognition and Biosensing, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China
| | - Xiaoxuan Yu
- State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Molecular Recognition and Biosensing, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China
| | - Rui Du
- State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Molecular Recognition and Biosensing, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China
| | - Xiaoqin Hong
- State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Molecular Recognition and Biosensing, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China
| | - Guangming Liu
- Department of Urology, Tianjin First Center Hospital, Nankai University, Tianjin 300071, China
| | - Hongmei Gao
- Department of Intensive Care Unit, Key Laboratory for Critical Care Medicine of the Ministry of Health, Emergency Medicine Research Institute, Tianjin First Center Hospital, Nankai University, Tianjin 300071, China
| | - Dingbin Liu
- State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Molecular Recognition and Biosensing, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China
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Shi J, Lin Z, Zheng Z, Chen M, Huang X, Wang J, Li M, Shao J. Glutamine metabolism promotes human trophoblast cell invasion via COL1A1 mediated by PI3K-AKT pathway. J Reprod Immunol 2024; 166:104321. [PMID: 39243705 DOI: 10.1016/j.jri.2024.104321] [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: 03/21/2024] [Revised: 07/13/2024] [Accepted: 08/19/2024] [Indexed: 09/09/2024]
Abstract
Abnormal trophoblast invasion function is an important cause of recurrent spontaneous abortion (RSA). Recent research has revealed a connection between glutamine metabolism and RSA. However, the interplay between these three factors and their related mechanisms remains unclear. To address this issue, we collected villus tissues from 10 healthy women with induced abortion and from 10 women with RSA to detect glutamine metabolism. Then, the trophoblast cell line HTR-8/SVneo was used in vitro to explore the effect of glutamine metabolism on trophoblast cells invasion, which was tested by transwell assay. We found that the concentration of glutamine in the villi of the normal pregnancy group was significantly higher than that in the RSA group. Correspondingly, the expression levels of key enzymes involved in glutamine synthesis and catabolism, including glutamine synthetase and glutaminase, were significantly higher in the villi of the normal pregnancy group. Regarding trophoblast cells, glutamine markedly enhanced the proliferative and invasive abilities of HTR-8/SVneo cells. Additionally, collagen type I alpha 1 (COL1A1) was confirmed to be a downstream target of glutamine, and glutamine also activated the PI3K-AKT pathway in HTR-8/SVneo cells. These findings indicate that glutamine metabolism facilitates the invasion of trophoblasts by up-regulating COL1A1 expression through the activation of the PI3K-AKT pathway, but the specific mechanism of COL1A1 requires further study.
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Affiliation(s)
- Jialu Shi
- Department of Gynecology, Hospital of Obstetrics and Gynecology, Shanghai Medical School, Fudan University, Shanghai 200090, China
| | - Zhi Lin
- Department of Gynecology, Hospital of Obstetrics and Gynecology, Shanghai Medical School, Fudan University, Shanghai 200090, China
| | - Zimeng Zheng
- Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Shanghai Medical School, Fudan University, Shanghai 200080, China
| | - Min Chen
- Department of Ultrasound, Women's Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province 310000, China
| | - Xu Huang
- Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Shanghai Medical School, Fudan University, Shanghai 200080, China
| | - Jiarui Wang
- Shanghai Medical School, Fudan University, Shanghai 200032, China
| | - Mingqing Li
- Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Shanghai Medical School, Fudan University, Shanghai 200080, China.
| | - Jun Shao
- Department of Gynecology, Hospital of Obstetrics and Gynecology, Shanghai Medical School, Fudan University, Shanghai 200090, China.
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Xu Y, Jin H, Chen Y, Yang Z, Xu D, Zhang X, Yang J, Wang Y. Comprehensive analysis of the expression, prognostic, and immune infiltration for COL4s in stomach adenocarcinoma. BMC Med Genomics 2024; 17:168. [PMID: 38907304 PMCID: PMC11191235 DOI: 10.1186/s12920-024-01934-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Accepted: 06/14/2024] [Indexed: 06/23/2024] Open
Abstract
BACKGROUND Collagen (COL) genes, play a key role in tumor invasion and metastasis, are involved in tumor extracellular matrix (ECM)-receptor interactions and focal adhesion pathways. However, studies focusing on the diagnostic value of the COL4 family in stomach adenocarcinoma (STAD) are currently lacking. METHODS The TCGA database was employed to retrieve the clinical features and RNA sequencing expression profiles of patients with STAD. We conducted an investigation to examine the expression disparities between STAD and adjacent normal tissues. Kaplan-Meier survival analysis was utilized to assess their prognostic significance, while Spearman correlation analysis was employed to determine their association with immune checkpoint genes and immunomodulatory molecules. Furthermore, GO and KEGG analyses were performed on the COL4s-related genes, revealing potential biological pathways through gene set enrichment analysis (GSEA). Subsequently, we explored the extent of immune infiltration of the COL4 family in STAD using the TIMER database. Lastly, the expression levels of the COL4 family in STAD were further validated through quantitative PCR (qPCR) and western blot techniques. RESULTS The expression levels of COL4A1/2 were significantly upregulated, while COL4A5/6 were conspicuously downregulated in STAD. The survival analysis revealed that the upregulated COL4s indicated poorer overall survival, first progression and post-progression survival outcomes. Additionally, our findings demonstrated a positive correlation between the expressions of COL4A1/2/3/4 and the infiltration of immune cells, including CD8 + T cells, dendritic cells, macrophages, neutrophils and CD4 + T cells. Further correlation analysis uncovered a favorable association between the expression of COL4A1/2/3/4 and various crucial immunomodulatory molecules, immunological checkpoint molecules, and chemokines. Quantitative PCR analysis confirmed that the expression patterns of COL4A1/3/4/6 genes aligned with the finding from the TCGA database. However, gastric cancer cells exhibited downregulation of COL4A2. Consistently, the protein level of COL4A1 was elevated, whereas the protein level of COL4A2 was reduced in the gastric cancer cell lines. CONCLUSION COL4s could potentially serve as biomarkers for diagnosing and predicting the prognosis of STAD.
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Affiliation(s)
- Ying Xu
- Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou, China
- Hangzhou Institute of Digestive Diseases, Hangzhou, China
- Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, China
| | - Hangbin Jin
- Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou, China
- Hangzhou Institute of Digestive Diseases, Hangzhou, China
- Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, China
- Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Hangzhou, Zhejiang, China
| | - Yan Chen
- Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou, China
- Hangzhou Institute of Digestive Diseases, Hangzhou, China
- Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, China
| | - Zhen Yang
- School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Dongchao Xu
- Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou, China
- Hangzhou Institute of Digestive Diseases, Hangzhou, China
- Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, China
| | - Xiaofeng Zhang
- Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou, China.
- Hangzhou Institute of Digestive Diseases, Hangzhou, China.
- Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, China.
- Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Hangzhou, Zhejiang, China.
| | - Jianfeng Yang
- Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou, China.
- Hangzhou Institute of Digestive Diseases, Hangzhou, China.
- Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, China.
- Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Hangzhou, Zhejiang, China.
| | - Yu Wang
- Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou, China.
- Hangzhou Institute of Digestive Diseases, Hangzhou, China.
- Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, China.
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Abdolahi F, Shahraki A, Sheervalilou R, Mortazavi SS. Identification of differentially expressed genes associated with the pathogenesis of gastric cancer by bioinformatics analysis. BMC Med Genomics 2023; 16:311. [PMID: 38041130 PMCID: PMC10690994 DOI: 10.1186/s12920-023-01720-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Accepted: 10/29/2023] [Indexed: 12/03/2023] Open
Abstract
AIM Gastric cancer (GC) is one of the most diagnosed cancers worldwide. GC is a heterogeneous disease whose pathogenesis has not been entirely understood. Besides, the GC prognosis for patients remains poor. Hence, finding reliable biomarkers and therapeutic targets for GC patients is urgently needed. METHODS GSE54129 and GSE26942 datasets were downloaded from Gene Expression Omnibus (GEO) database to detect differentially expressed genes (DEGs). Then, gene set enrichment analyses and protein-protein interactions were investigated. Afterward, ten hub genes were identified from the constructed network of DEGs. Then, the expression of hub genes in GC was validated. Performing survival analysis, the prognostic value of each hub gene in GC samples was investigated. Finally, the databases were used to predict microRNAs that could regulate the hub genes. Eventually, top miRNAs with more interactions with the list of hub genes were introduced. RESULTS In total, 203 overlapping DEGs were identified between both datasets. The main enriched KEGG pathway was "Protein digestion and absorption." The most significant identified GO terms included "primary alcohol metabolic process," "basal part of cell," and "extracellular matrix structural constituent conferring tensile strength." Identified hub modules were COL1A1, COL1A2, TIMP1, SPP1, COL5A2, THBS2, COL4A1, MUC6, CXCL8, and BGN. The overexpression of seven hub genes was associated with overall survival. Moreover, among the list of selected miRNAs, hsa-miR-27a-3, hsa-miR-941, hsa-miR-129-2-3p, and hsa-miR-1-3p, were introduced as top miRNAs targeting more than five hub genes. CONCLUSIONS The present study identified ten genes associated with GC, which may help discover novel prognostic and diagnostic biomarkers as well as therapeutic targets for GC. Our results may advance the understanding of GC occurrence and progression.
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Affiliation(s)
- Fatemeh Abdolahi
- Department of Biology, Faculty of Science, University of Sistan and Baluchestan, Zahedan, Iran
| | - Ali Shahraki
- Department of Biology, Faculty of Science, University of Sistan and Baluchestan, Zahedan, Iran
| | - Roghayeh Sheervalilou
- Pharmacology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.
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Zhou J, Xiang H, Cao Z. Dual mechanism of Let-7i in tumor progression. Front Oncol 2023; 13:1253191. [PMID: 37829341 PMCID: PMC10565035 DOI: 10.3389/fonc.2023.1253191] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Accepted: 09/06/2023] [Indexed: 10/14/2023] Open
Abstract
Let-7i regulates tumors primarily by binding to the 3' untranslated region (3' UTR) of mRNA, which indirectly regulates post-transcriptional gene expression. Let-7i also has an epigenetic function via modulating DNA methylation to directly regulate gene expression. Let-7i performs a dual role by inducing both the promotion and inhibition of various malignancies, depending on its target. The mechanism of Let-7i action involves cancer cell proliferation, migration, invasion, apoptosis, epithelial-mesenchymal transition, EV transmission, angiogenesis, autophagy, and drug resistance sensitization. Let-7i is closely related to cancer, and hence, is a potential biomarker for the diagnosis and prognosis of various cancers. Therapeutically, it can be used to promote an anti-cancer immune response by modifying exosomes, thus exerting a tumor-suppressive effect.
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Affiliation(s)
- Jiapei Zhou
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Hongjie Xiang
- Department of Traditional Chinese Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China
| | - Zhiqun Cao
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
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Ding B, Ye Z, Yin H, Hong XY, Feng SW, Xu JY, Shen Y. Exosomes derived from ovarian cancer cells regulate proliferation and migration of cancer-associated fibroblasts. Genomics 2023; 115:110703. [PMID: 37678440 DOI: 10.1016/j.ygeno.2023.110703] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Revised: 06/16/2023] [Accepted: 09/04/2023] [Indexed: 09/09/2023]
Abstract
Cancer-associated fibroblast (CAF) is an essential risk factor for ovarian cancer. Exosomes can mediate cellular communication in the tumour microenvironment, but the interaction of tumour cell exosomes with CAF is less studied in Ovarian cancer. This study identified H19/miR-29c-3p/LOXL2-COL1A1 as a ceRNA regulatory network involved in regulating tumour matrix-associated signaling pathways associated with CAF. Cellular assays demonstrated that exosomes from ovarian cancer cell line SKOV3 significantly promoted the proliferation and migration of CAF. The results of mixed transplantation tumour experiments in nude mice showed that exosomes of SKOV3 significantly promoted tumour growth. Ovarian cancer tumour-derived exosomes can regulate CAF proliferation and migration through H19/miR-29c-3p/LOXL2-COL1A1. This study reveals the regulatory role of tumour exosomes on CAF, which may provide a theoretical basis for the development of therapeutic regimens targeting fibroblasts in ovarian cancer.
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Affiliation(s)
- Bo Ding
- Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Zheng Ye
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China
| | - Han Yin
- Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Xin-Yi Hong
- Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Song-Wei Feng
- Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Jing-Yun Xu
- Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Yang Shen
- Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
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Hou J, Sun X. Let -7i : A key player and a promising biomarker in diseases. ZHONG NAN DA XUE XUE BAO. YI XUE BAN = JOURNAL OF CENTRAL SOUTH UNIVERSITY. MEDICAL SCIENCES 2023; 48:909-919. [PMID: 37587077 PMCID: PMC10930445 DOI: 10.11817/j.issn.1672-7347.2023.220146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Indexed: 08/18/2023]
Abstract
MicroRNAs (miRNAs) are endogenous non-coding single-stranded small RNAs that regulate gene expression by recognizing homologous sequences and interfering with transcriptional, translational or epigenetic processes. MiRNAs are involved in a variety of disease processes, and regulate the physiological and pathological status of diseases by modulating target cell activity, migration, invasion, apoptosis, autophagy and other processes. Among them, let-7i is highly expressed in various systems, which participates in the process of tumors, cardiovascular and cerebrovascular diseases, fibrotic diseases, inflammatory diseases, neurodegenerative diseases and other diseases, and plays a positive or negative regulatory role in these diseases through different signal pathways and key molecules. Moreover, it can be used as an early diagnosis and prognostic marker for a variety of diseases and become a potential therapeutic target. As a biomarker, let-7i is frequently tested in combination with other miRNAs to diagnose multiple diseases and evaluate the clinical treatment or prognosis.
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Affiliation(s)
- Jiali Hou
- Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Sciences, Central South University, Changsha 410078.
- National Engineering Research Center of Human Stem Cells, Changsha 410205, China.
| | - Xuan Sun
- Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Sciences, Central South University, Changsha 410078.
- National Engineering Research Center of Human Stem Cells, Changsha 410205, China.
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Gareev I, Ahmad A, Wang J, Beilerli A, Ilyasova T, Sufianov A, Beylerli O. Gastric juice non-coding RNAs as potential biomarkers for gastric cancer. Front Physiol 2023; 14:1179582. [PMID: 37179825 PMCID: PMC10169709 DOI: 10.3389/fphys.2023.1179582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Accepted: 04/18/2023] [Indexed: 05/15/2023] Open
Abstract
Gastric cancer (GC), being one of the most common malignant human tumors, occupies the second position in the structure of mortality in men and women. High rates of morbidity and mortality in this pathology determine its extremely high clinical and social significance. Diagnosis and timely treatment of precancerous pathology is the main way to reduce morbidity and mortality, and early detection of GC and its adequate treatment improve prognosis. The ability to accurately predict the development of GC and start treatment on time, as well as the ability to determine the stage of the disease if the diagnosis is confirmed - non-invasive biomarkers can become the key to solving these and many other problems of modern medicine. One of the promising biomarkers being studied are non-coding RNAs, namely, miсroRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). They are involved in a wide range of processes, including apoptosis, proliferation, differentiation, angiogenesis, which play a critical role in the development of GC oncogenesis. In addition, they are quite specific and stable due to their carriers (extracellular vesicles or Argonaute 2 protein) and can be detected in various human biological fluids, in particular gastric juice. Thus, miRNAs, lncRNAs, and circRNAs isolated from the gastric juice of GC patients are promising preventive, diagnostic and prognostic non-invasive biomarkers. This review article presents the characteristics of circulating or extracellular miRNAs, lncRNAs, and circRNAs in gastric juice, allowing their use in the GC preventive, diagnosis, prognosis and monitoring therapy.
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Affiliation(s)
- Ilgiz Gareev
- Educational and Scientific Institute of Neurosurgery, Peoples’ Friendship University of Russia (RUDN University), Moscow, Russian
| | - Aamir Ahmad
- Academic Health System, Hamad Medical Corporation, Interim Translational Research Institute, Doha, Qatar
| | - Jiaqi Wang
- Department of Urology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Aferin Beilerli
- Department of Obstetrics and Gynecology, Tyumen State Medical University, Tyumen, Russia
| | - Tatiana Ilyasova
- Department of Internal Diseases, Bashkir State Medical University, Ufa, Russia
| | - Albert Sufianov
- Educational and Scientific Institute of Neurosurgery, Peoples’ Friendship University of Russia (RUDN University), Moscow, Russian
- Department of Neurosurgery, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Ozal Beylerli
- Educational and Scientific Institute of Neurosurgery, Peoples’ Friendship University of Russia (RUDN University), Moscow, Russian
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10
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Wang Y, Bai H, Jiang M, Zhou C, Gong Z. Emerging role of long non-coding RNA JPX in malignant processes and potential applications in cancers. Chin Med J (Engl) 2023; 136:757-766. [PMID: 37027401 PMCID: PMC10150895 DOI: 10.1097/cm9.0000000000002392] [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: 05/06/2022] [Indexed: 04/08/2023] Open
Abstract
Long non-coding RNAs (lncRNAs) reportedly function as important modulators of gene regulation and malignant processes in the development of human cancers. The lncRNA JPX is a novel molecular switch for X chromosome inactivation and differentially expressed JPX has exhibited certain clinical correlations in several cancers. Notably, JPX participates in cancer growth, metastasis, and chemoresistance, by acting as a competing endogenous RNA for microRNA, interacting with proteins, and regulating some specific signaling pathways. Moreover, JPX may serve as a potential biomarker and therapeutic target for the diagnosis, prognosis, and treatment of cancer. The present article summarizes our current understanding of the structure, expression, and function of JPX in malignant cancer processes and discusses its molecular mechanisms and potential applications in cancer biology and medicine.
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Affiliation(s)
- Yuanyuan Wang
- Department of Clinical Medicine, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, China
| | - Huihui Bai
- Department of Biochemistry and Molecular Biology, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, China
- Zhejiang Province Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, China
| | - Meina Jiang
- Department of Biochemistry and Molecular Biology, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, China
- Zhejiang Province Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, China
| | - Chengwei Zhou
- Department of Clinical Medicine, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, China
- Department of Thoracic Surgery, The Affiliated Hospital of Ningbo University School of Medicine, Ningbo, Zhejiang 315020, China
| | - Zhaohui Gong
- Department of Clinical Medicine, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, China
- Department of Biochemistry and Molecular Biology, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, China
- Zhejiang Province Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, China
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11
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Majed SO, Mustafa SA. The profiles of miR-4510 expression level in breast cancer. Sci Rep 2023; 13:2262. [PMID: 36755123 PMCID: PMC9908886 DOI: 10.1038/s41598-022-25292-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Accepted: 11/28/2022] [Indexed: 02/10/2023] Open
Abstract
MicroRNA that is abnormally produced in breast cells can disrupt biological processes, which can lead to cancer. This study aims to screen differentially expressed genes (DEGs) and ncRNAs (DEncRNAs) in the formalin-fixed paraffin-embedded (FFPE) tissues of breast cancer (BC) as compared with the normal adjacent tissues (NAT), and identify miR-4510 as a novel biomarker of BC. This study looked at differentially expressed genes (DEGs) using MACE-Seq and differentially expressed ncRNAs (DEncRNAs) using the small RNA-Seq. Real-time qPCR was used to determine the level of expression of miR-4510. In this study, MACE-Seq results showed that 26,795 genes, with a p-value < 0.05, were differentially expressed in BC paraffin tissues as compared with NAT. Small RNA-Seq results revealed that 1326 ncRNAs, with a p-value < 0.05, were differentially expressed. We confirmed that miR-4510 was significantly down-expressed (p-value = 0.001) by qRT-PCR in the paraffin tissue of 120 BC patients. Based on eleven computational prediction programs, TP53, TP53INP1, MMP11, and COL1A1 for the miR-4510 were identified as miR-4510 targets. The MACE-seq result showed that the gene of TP53 (p-value = 0.001) and TP53INP1 (p-value = 0.02) was significantly down-regulated, but the gene of MMP11 (p-value = 0.004) and COL1A1 (p-value = 0.0001) was significantly over-expressed in 20 paired specimens of the BC and NAT. We discovered that a single SNP inside the miR-4510 binding site occurred only in BC, in which Guanine (G) changed into Adenine (A). Two SNPs outside the miR-4510 binding site occurred, and Guanine (G) in both BC and NAT was changed into Thymine (T), as compared to the reference sequence (RefSeq). Overall, our results suggested that miR-4510 functions as a tumor suppressor in the BC. Mir-4510 may act as a tumor suppressor, however additional experimental data is needed to corroborate these assumptions and can be exploited as a biomarker for BC.
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Affiliation(s)
- Sevan Omer Majed
- Biology Department, College of Education, Salahaddin University-Erbil, Erbil, Iraq
| | - Suhad Asad Mustafa
- General Directorate of Scientific Research Center, Salahaddin University-Erbil, Erbil, Iraq.
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12
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Kim K, Kim YJ. RhoBTB3 Regulates Proliferation and Invasion of Breast Cancer Cells via Col1a1. Mol Cells 2022; 45:631-639. [PMID: 35698915 PMCID: PMC9448648 DOI: 10.14348/molcells.2022.2037] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 04/28/2022] [Accepted: 05/09/2022] [Indexed: 11/27/2022] Open
Abstract
Breast cancer is the leading cause of cancer-related death in women worldwide, despite medical and technological advancements. The RhoBTB family consists of three isoforms: RhoBTB1, RhoBTB2, and RhoBTB3. RhoBTB1 and RhoBTB2 have been proposed as tumor suppressors in breast cancer. However, the roles of RhoBTB3 proteins are unknown in breast cancer. Bioinformatics analysis, including Oncomine, cBioportal, was used to evaluate the potential functions and prognostic values of RhoBTB3 and Col1a1 in breast cancer. qRT-PCR analysis and immunoblotting assay were performed to investigate relevant expression. Functional experiments including proliferation assay, invasion assay, and flow cytometry assay were conducted to determine the role of RhoBTB3 and Col1a1 in breast cancer cells. RhoBTB3 mRNA levels were significantly up-regulated in breast cancer tissues as compared to in adjacent normal tissues. Moreover, RhoBTB3 expression was found to be associated with Col1a1 expression. Decreasing RhoBTB3 expression may lead to decreases in the proliferative and invasive properties of breast cancer cells. Further, Col1a1 knockdown in breast cancer cells limited the proliferative and invasive ability of cancer cells. Knockdown of RhoBTB3 may exert inhibit the proliferation, migration, and metastasis of breast cancer cells by repressing the expression of Col1a1, providing a novel therapeutic strategy for treating breast cancer.
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Affiliation(s)
- Kyungho Kim
- Targeted Therapy Branch, Division of Rare and Refractory Cancer, Research Institute, National Cancer Center, Goyang 10408, Korea
| | - Youn-Jae Kim
- Targeted Therapy Branch, Division of Rare and Refractory Cancer, Research Institute, National Cancer Center, Goyang 10408, Korea
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13
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Lu J, Li R, Fang M, Ke S. Hub Genes and Long Noncoding RNAs That Regulates It Associated with the Prognosis of Esophageal Squamous Cell Carcinoma Based on Bioinformatics Analysis. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:6027058. [PMID: 36238478 PMCID: PMC9553368 DOI: 10.1155/2022/6027058] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Accepted: 08/27/2022] [Indexed: 12/09/2022]
Abstract
Objective Through bioinformatics analysis methods, the public databases GEO and TCGA were used to research mRNA and squamous cell carcinoma of the esophagus, construct a lncRNA-mRNA network, and screen hub genes and lncRNAs related to prognosis. Method Download esophageal squamous cell carcinoma-related mRNA and lncRNA datasets GEO and TCGA public datasets, as well as clinical data, use bioinformatic tools to perform gene differential expression analysis on the datasets to obtain differentially expressing mRNA (DEmRNA) and lncRNA (DElncRNA), and plot volcano plots and cluster heatmaps. The differential intersection of differentially expressed DEmRNA and DElncRNA was extracted by Venn diagram and imported into CytoScape software, a regulatory network visualization software, to construct a lncRNA-mRNA network and use cytoHubba and MCODE plug-ins to screen hub genes and key lncRNAs. The DEmRNA in the network was imported into the Gene and Protein Interaction Retrieval Database (STRING), gene-encoded protein-protein interactions (PPI) network maps were created, and the genes in the PPI network maps were submitted to GO functional annotation and pathway enrichment analysis using Kyoto Encyclopedia of Gene Genomes (KEGG) (KEGG). The link between hub gene and prognosis was studied using the clinical data collected by TCGA. Result Retrieve the datasets GSE23400 and GSE38129 from the GEO database and the esophageal squamous cell carcinoma-related mRNAs from TCGA databases and then obtain intersection. Differentially regulated genes revealed a correlation of 326 (up) with 191 (down) in terms of the differential intersection; for this study, we need to collect the GSE130078 dataset from GEO, as well as the lncRNAs from TCGA databases that are connected to esophageal squamous cell cancer. There were 184 differentially up- and downregulated genes in the differential intersection. A differential intersection network of the differential intersection lncRNA-mRNA network allowed us to identify the hub genes, including COL5A2 (COL3A1), COL1A1 (COL1A1), CTD-2171N6.1 (CTD-2171N6.1), and RP11-863P13.3 (RP11-863P13.3). The extracellular matrix, which is important in protein digestion and absorption, was shown to be the primary site of functional enrichment, as shown by GO/KEGG analysis. Squamous cell carcinoma of the mouth and throat is associated with a poor prognosis because of a change in the extracellular matrix structure caused by specific long noncoding RNA (lncRNA) regulatory upregulation. Conclusion For the purpose of predicting the prognosis of cancer of the esophagus, researchers studied the esophageal squamous cell carcinoma-related hub genes and important noncoding RNAs (ncRNAs).
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Affiliation(s)
- Jun Lu
- Department of Emergency Medicine & Intensive Care Unit, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Ruichao Li
- Department of General Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Minghao Fang
- Department of Emergency Medicine & Intensive Care Unit, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Shun Ke
- Department of Emergency Medicine & Intensive Care Unit, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
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14
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Li X, Sun X, Kan C, Chen B, Qu N, Hou N, Liu Y, Han F. COL1A1: A novel oncogenic gene and therapeutic target in malignancies. Pathol Res Pract 2022; 236:154013. [PMID: 35816922 DOI: 10.1016/j.prp.2022.154013] [Citation(s) in RCA: 52] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Revised: 06/28/2022] [Accepted: 07/04/2022] [Indexed: 02/07/2023]
Abstract
Collagen type I alpha 1 (COL1A1), a member of the collagen family, is involved in epithelial-mesenchymal transition, which is closely linked to malignant tumorigenesis. COL1A1 is highly expressed in various cancers and regulates various cellular processes, including cell proliferation, metastasis, apoptosis, and cisplatin resistance. COL1A1 is also associated with cancer progression and prognosis; elevated COL1A1 expression is associated with poor prognosis in cancer patients. However, the main role of COL1A as a cancer-promoting factor in specific tumors has not been reported. Additionally, the protein levels and mechanisms of action of this protein differ among tumor types. This review discusses current research progress concerning COL1A1 in different tumor types, and then summarizes its contributions to cancer progression, thus providing a basis for follow-up research and potential targets for cancer treatment.
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Affiliation(s)
- Xue Li
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China; Department of Pathology, Affiliated Hospital of Weifang Medical University, Weifang, China; Branch of Shandong Provincial Clinical Research Center for Diabetes and Metabolic Diseases, and Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Xiaodong Sun
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China; Branch of Shandong Provincial Clinical Research Center for Diabetes and Metabolic Diseases, and Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Chengxia Kan
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China; Branch of Shandong Provincial Clinical Research Center for Diabetes and Metabolic Diseases, and Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Bing Chen
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China; Department of Pathology, Affiliated Hospital of Weifang Medical University, Weifang, China; Branch of Shandong Provincial Clinical Research Center for Diabetes and Metabolic Diseases, and Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Na Qu
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China; Department of Pathology, Affiliated Hospital of Weifang Medical University, Weifang, China; Branch of Shandong Provincial Clinical Research Center for Diabetes and Metabolic Diseases, and Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Ningning Hou
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China; Branch of Shandong Provincial Clinical Research Center for Diabetes and Metabolic Diseases, and Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Yongping Liu
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China; Branch of Shandong Provincial Clinical Research Center for Diabetes and Metabolic Diseases, and Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China.
| | - Fang Han
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China; Department of Pathology, Affiliated Hospital of Weifang Medical University, Weifang, China; Branch of Shandong Provincial Clinical Research Center for Diabetes and Metabolic Diseases, and Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China.
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15
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Tu F, Li M, Chen Y, Chu H, Wang S, Hai L, Xie T, Geng F, Zhao T, Wang Q, Feng Z. Let-7i-3p inhibits the cell cycle, proliferation, invasion, and migration of colorectal cancer cells via downregulating CCND1. Open Med (Wars) 2022; 17:1019-1030. [PMID: 35795002 PMCID: PMC9175015 DOI: 10.1515/med-2022-0499] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 05/14/2022] [Accepted: 05/15/2022] [Indexed: 12/24/2022] Open
Abstract
Dysregulated microRNAs are closely related to the malignant progression of colorectal cancer (CRC). Although abnormal let-7i-3p expression has been reported in various human cancers, its biological role and potential mechanism in CRC remain unclear. Therefore, the purpose of this study was to investigate the expression and regulation of let-7i-3p in CRC. Here, we demonstrated that let-7i-3p expression was significantly downregulated in three CRC cell lines while CyclinD1 (CCND1) was upregulated compared with the normal colon epithelial FHC cells. Moreover, bioinformatics and luciferase reporter assays revealed that CCND1 was a direct functional target of let-7i-3p. In addition, let-7i-3p overexpression or CCND1 silencing inhibited cell cycle, proliferation, invasion, and migration and diminished the activation of p-ERK in HCT116 cells. However, exogenously expressing CCND1 alleviated these effects. Taken together, our findings may provide new insight into the pathogenesis of CRC and let-7i-3p/CCND1 might function as new therapeutic targets for CRC.
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Affiliation(s)
- Fei Tu
- Department of Anatomy, Histology & Embryology, School of Basic Medical Sciences, Xinxiang Medical University , Xinxiang , China
- Institute of Precision Medicine, Xinxiang Medical University , Xinxiang , China
- School of Forensic Medicine, Xinxiang Medical University , Xinxiang , China
| | - Mengfan Li
- Department of Anatomy, Histology & Embryology, School of Basic Medical Sciences, Xinxiang Medical University , Xinxiang , China
| | - Yinyu Chen
- Department of Anatomy, Histology & Embryology, School of Basic Medical Sciences, Xinxiang Medical University , Xinxiang , China
| | - Huiru Chu
- Department of Anatomy, Histology & Embryology, School of Basic Medical Sciences, Xinxiang Medical University , Xinxiang , China
| | - Shujie Wang
- Department of Anatomy, Histology & Embryology, School of Basic Medical Sciences, Xinxiang Medical University , Xinxiang , China
| | - Lun Hai
- The First Affiliated Hospital of Xinxiang Medical University , Weihui , China
| | - Ting Xie
- Department of Anatomy, Histology & Embryology, School of Basic Medical Sciences, Xinxiang Medical University , Xinxiang , China
| | - Fangfang Geng
- Department of Anatomy, Histology & Embryology, School of Basic Medical Sciences, Xinxiang Medical University , Xinxiang , China
| | - Tiesuo Zhao
- Institute of Precision Medicine, Xinxiang Medical University , Xinxiang , China
- Department of Immunology, School of Basic Medical Sciences, Xinxiang Medical University , Xinxiang , China
| | - Qingzhi Wang
- Department of Anatomy, Histology & Embryology, School of Basic Medical Sciences, Xinxiang Medical University , Xinxiang , China
| | - Zhiwei Feng
- Department of Anatomy, Histology & Embryology, School of Basic Medical Sciences, Xinxiang Medical University , Xinxiang , China
- Institute of Precision Medicine, Xinxiang Medical University , Xinxiang , China
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16
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Wang C, Wang Y, Fu Z, Huang W, Yu Z, Wang J, Zheng K, Zhang S, Li S, Chen J. MiR-29b-3p Inhibits Migration and Invasion of Papillary Thyroid Carcinoma by Downregulating COL1A1 and COL5A1. Front Oncol 2022; 12:837581. [PMID: 35530352 PMCID: PMC9075584 DOI: 10.3389/fonc.2022.837581] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 03/16/2022] [Indexed: 11/13/2022] Open
Abstract
INTRODUCTION MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate genetic expression and are also vital for tumor initiation and development. MiR-29b-3p was found to be involved in regulating various biological processes of tumors, including tumor cell proliferation, metastasis, and apoptosis inhibition; however, the biofunction and molecule-level mechanisms of miR-29b-3p inpapillary thyroid carcinoma (PTC) remain unclear. METHODS The expression of miR-29b-3p in PTC samples was tested via qRT-PCR. Cellular proliferation was analyzed by CCK-8 and EdU assays, and cellular migratory and invasive abilities were assessed utilizing wound-healing and Transwell assays. In addition, protein expressions of COL1A1, COL5A1, E-cadherin, N-cadherin, Snail, and Vimentin were identified via Western blot (WB) assay. Bioinformatics, qRT-PCR, WB, and dual luciferase reporter assays were completed to identify whether miR-29b-3p targeted COL1A1 and COL5A1. In addition, our team explored the treatment effects of miR-29b-3p on a murine heterograft model. RESULTS Our findings revealed that miR-29b-3p proved much more regulated downward in PTC tissue specimens than in adjacent non-cancerous tissues. Meanwhile, decreased expression of miR-29b-3p was strongly related to the TNM stage of PTC patients (p<0.001), while overexpression of miR-29b-3p in PTC cells suppressed cellular migration, invasion, proliferation, and EMT. Conversely, silencing miR-29b-3p yielded the opposite effect. COL1A1 and COL5A1 were affirmed as the target of miR-29b-3p. Additionally, the COL1A1 and COL5A1 were highly expressed in PTC tumor samples than in contrast to neighboring healthy samples. Functional assays revealed that overexpression of COL1A1 or COL5A1 reversed the suppressive role of miR-29b-3p in migration, invasion, and EMT of PTC cells. Finally, miR-29b-3p agomir treatment dramatically inhibited Xenograft tumor growth in the animal model. CONCLUSIONS These findings document that miR-29b-3p inhibited PTC cells invasion and metastasis by targeting COL1A1 and COL5A1; this study also sparks new ideas for risk assessment and miRNA replacement therapy in PTC.
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Affiliation(s)
- Congjun Wang
- Department of Gastrointestinal Gland Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Clinical Research Lab, Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, China
| | - Ye Wang
- Department of Gastrointestinal Gland Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Clinical Research Lab, Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, China
| | - Zhao Fu
- Department of Gastrointestinal Gland Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Clinical Research Lab, Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, China
| | - Weijia Huang
- Department of Gastrointestinal Gland Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Clinical Research Lab, Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, China
| | - Zhu Yu
- Department of Gastrointestinal Gland Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Clinical Research Lab, Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, China
| | - Jiancheng Wang
- Department of Gastrointestinal Gland Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Clinical Research Lab, Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, China
| | - Kaitian Zheng
- Department of Gastrointestinal Gland Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Clinical Research Lab, Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, China
| | - Siwen Zhang
- Department of Gastrointestinal Gland Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Clinical Research Lab, Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, China
| | - Shen Li
- Department of Gastrointestinal, Hernia and Enterofistula Surgery, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Junqiang Chen
- Department of Gastrointestinal Gland Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Clinical Research Lab, Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, China
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Tang SY, Zhou PJ, Meng Y, Zeng FR, Deng GT. Gastric cancer: An epigenetic view. World J Gastrointest Oncol 2022; 14:90-109. [PMID: 35116105 PMCID: PMC8790429 DOI: 10.4251/wjgo.v14.i1.90] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Revised: 05/17/2021] [Accepted: 12/23/2021] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer (GC) poses a serious threat worldwide with unfavorable prognosis mainly due to late diagnosis and limited therapies. Therefore, precise molecular classification and search for potential targets are required for diagnosis and treatment, as GC is complicated and heterogeneous in nature. Accumulating evidence indicates that epigenetics plays a vital role in gastric carcinogenesis and progression, including histone modifications, DNA methylation and non-coding RNAs. Epigenetic biomarkers and drugs are currently under intensive evaluations to ensure efficient clinical utility in GC. In this review, key epigenetic alterations and related functions and mechanisms are summarized in GC. We focus on integration of existing epigenetic findings in GC for the bench-to-bedside translation of some pivotal epigenetic alterations into clinical practice and also describe the vacant field waiting for investigation.
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Affiliation(s)
- Si-Yuan Tang
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Pei-Jun Zhou
- Cancer Research Institute, School of Basic Medicine Science, Central South University, School of Basic Medicine Science, Central South University 410008, Hunan Province, China
| | - Yu Meng
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Fu-Rong Zeng
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Guang-Tong Deng
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
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18
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Wu X, Wang H, Zhu D, Chai Y, Wang J, Dai W, Xiao Y, Tang W, Li J, Hong L, Pei M, Zhang J, Lin Z, Wang J, Li A, Liu S. USP3 promotes gastric cancer progression and metastasis by deubiquitination-dependent COL9A3/COL6A5 stabilisation. Cell Death Dis 2021; 13:10. [PMID: 34930901 PMCID: PMC8688524 DOI: 10.1038/s41419-021-04460-7] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 11/22/2021] [Accepted: 12/07/2021] [Indexed: 11/09/2022]
Abstract
As an important regulator of intracellular protein degradation, the mechanism of the deubiquitinating enzyme family in tumour metastasis has received increasing attention. Our previous study revealed that USP3 promotes tumour progression and is highly expressed in gastric cancer (GC). Herein, we report two critical targets, COL9A3 and COL6A5, downstream of USP3, via the isobaric tags for relative and absolute quantification technique. Mechanistically, we observed that USP3 interacted with and stabilised COL9A3 and COL6A5 via deubiquitination in GC. Importantly, we found that COL9A3 and COL6A5 were essential mediators of USP3-modulated oncogenic activity in vitro and in vivo. Examination of clinical samples confirmed that elevated expression of USP3, concomitant with increased COL9A3 and COL6A5 abundance, correlates with human GC progression. These data suggest that USP3 promotes GC progression and metastasis by deubiquitinating COL9A3 and COL6A5. These findings identify a mechanism of GC metastasis regarding USP3-mediated deubiquitinating enzyme activity and suggest potential therapeutic targets for GC management.
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Affiliation(s)
- Xiaosheng Wu
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Hao Wang
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
- Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Guangzhou, 510515, China
| | - Danping Zhu
- Department of Medical Examination, Rocket Army Guangzhou Special Service Convalescent Center, Guangzhou, 510515, China
| | - Yixia Chai
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Jing Wang
- Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China
| | - Weiyu Dai
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Yizhi Xiao
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Weimei Tang
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Jiaying Li
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Linjie Hong
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Miaomiao Pei
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Jieming Zhang
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Zhizhao Lin
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Jide Wang
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
- Department of Gastroenterology, Longgang District People's Hospital, Shenzhen, 518172, China.
| | - Aimin Li
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
- Department of Gastroenterology, Longgang District People's Hospital, Shenzhen, 518172, China.
| | - Side Liu
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
- Department of Gastroenterology, Longgang District People's Hospital, Shenzhen, 518172, China.
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Lessi F, Aretini P, Rizzo M, Morelli M, Menicagli M, Franceschi S, Mazzanti CM. Analysis of exosome-derived microRNAs reveals insights of intercellular communication during invasion of breast, prostate and glioblastoma cancer cells. Cell Adh Migr 2021; 15:180-201. [PMID: 34157951 PMCID: PMC8224203 DOI: 10.1080/19336918.2021.1935407] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 04/08/2021] [Accepted: 05/20/2021] [Indexed: 12/28/2022] Open
Abstract
MiRNAs represent a mechanism that regulates gene expression in many pathological conditions. Exosomes are known to be secreted from all types of cells, and the exosomes-released molecules are crucial messengers that can regulate cellular processes. We investigated the miRNAs content of exosomes released by cancer cells during the invasion . An invasion stimulus has been generated through scratches created on the confluent cells of cancer cell lines: glioblastoma, breast and prostate cancers.Several miRNAs were found to be significantly differentially abundant during the cell invasion , both in common among different cell lines and exclusive. Understanding the language codes among cells involved in invasion can lead to the development of therapies that can inhibit cellular communication, slowing or eventually stopping their activity.
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Affiliation(s)
| | | | - Milena Rizzo
- Institute of Clinical Physiology (IFC), CNR, Pisa, Italy
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20
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Tang H, Long Q, Zhuang K, Han K, Zhang X, Guo H, Lu X. Retinoblastoma tumor suppressor gene 1 enhances 5-Fluorouracil chemosensitivity through SDF-1/CXCR4 axis by regulating autophagy in gastric cancer. Pathol Res Pract 2021; 224:153532. [PMID: 34214844 DOI: 10.1016/j.prp.2021.153532] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Revised: 06/18/2021] [Accepted: 06/18/2021] [Indexed: 11/29/2022]
Abstract
Due to lack of effective biomarkers for early diagnosis, most patients are diagnosed with advanced gastric cancer and have lower survival rates. 5-Fluorouracil (5-FU) is one of commonly used drugs for chemotherapy of gastric cancer, but drug resistance limits the wide application of agents. Retinoblastoma tumor suppressor gene 1 (RB1) is a key regulator in the progression of various human cancers, including gastric cancer. However, the effects of RB1 on chemosensitivity and the underlying mechanisms in gastric cancer (GC) are not clear. In this study, expressions of RB1 in GC cell lines were evaluated by RT-qPCR and western blot assay. CCK-8 was applied to examine the effect of 5-FU on cell viability. Meanwhile, IC50 values were calculated. The drug-resistance protein MDR1 and autophagy-related proteins were detected by western blot assay. Flow cytometry was used to detect cell cycle. The results showed that RB1 expressions were downregulated in GC cell lines and had significant differences between 5-FU resistance cell lines (SNU-620/5-FU and NUGC-3/5-FU) and non-resistance cell lines (SNU-620 and NUGC-3). Overexpression of RB1 enhanced 5-FU sensitivity of GC cells and caused cell cycle arrest in the S phase. Meanwhile, autophagy-related proteins were downregulated. Mechanistically, SDF-1/CXCR4 participated in the regulation of RB1 on cell autophagy. Autophagy activator, SDF-1 treatment and CXCR4 activation reversed the promoted effects of RB1 on 5-FU sensitivity in GC cells. In conclusion, our data revealed that RB1 was downregulated in GC cell lines. RB1 overexpression enhanced 5-FU chemosensitivity in GC cells by regulating cell autophagy via SDF-1/CXCR4 pathway. RB1 might serve as a promising therapeutic target of GC.
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Affiliation(s)
- Hailing Tang
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China; Department of Gastroenterology, Xi'an Central Hospital, Xi'an, Shaanxi 710003, China
| | - Qianfa Long
- Department of Neurosurgery, Xi'an Central Hospital, Xi'an, Shaanxi 710003, China
| | - Kun Zhuang
- Department of Gastroenterology, Xi'an Central Hospital, Xi'an, Shaanxi 710003, China
| | - Kun Han
- Department of Gastroenterology, Xi'an Central Hospital, Xi'an, Shaanxi 710003, China
| | - Xin Zhang
- Department of Gastroenterology, Xi'an Central Hospital, Xi'an, Shaanxi 710003, China
| | - Hanqing Guo
- Department of Gastroenterology, Xi'an Central Hospital, Xi'an, Shaanxi 710003, China
| | - Xiaolan Lu
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.
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21
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A Robust Circular RNA-Associated Three-Gene Prognostic Signature for Patients with Gastric Cancer. BIOMED RESEARCH INTERNATIONAL 2021; 2021:6633289. [PMID: 33969120 PMCID: PMC8084642 DOI: 10.1155/2021/6633289] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 03/23/2021] [Accepted: 04/01/2021] [Indexed: 01/17/2023]
Abstract
Accumulating evidence has demonstrated that circular RNAs (circRNAs) play vital roles in cancer progression. However, the underlying molecular mechanisms of circRNAs remain poorly elucidated in gastric cancer (GC). The main purpose of present study is to explore the underlying regulatory mechanism by constructing a circRNA-associated competitive endogenous RNA (ceRNA) network and further establish a robust prognostic signature for patients with GC. Based on expression data of circRNA, microRNA, and mRNA derived from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, a circRNA-associated ceRNA network, containing 15 cirRNAs, 9 microRNAs, and 35 mRNAs, was constructed using the Starbase database. Functional enrichment analysis showed that the ceRNA network might be involved in many cancer-related pathways, such as regulation of transcription from RNA polymerase II promoter, mesodermal cell differentiation, and focal adhesion. A protein-protein interaction network was constructed based on genes within the circRNA-associated ceRNA network. We found that six of ten hub genes within the PPI network were significantly associated with overall survival (OS). Thus, using the LASSO method, we constructed a three-gene prognostic signature based on TCGA-GC cohort, which could classify GC patients into low-risk and high-risk groups with significant difference in OS (HR = 1.9, 95%CI = 1.14‐3.2, and log-rank p = 0.001). The prognostic performance of the three-gene signature was verified in GSE15459 (HR = 1.9, 95%CI = 1.27‐3.0, and log − rank p = 2.2E − 05) and GSE84437 (HR = 1.5, 95%CI = 1.17‐2.0, and log − rank p = 6.3E − 04). Multivariate Cox analysis further revealed that the three-gene prognostic signature could serve as an independent risk factor for OS. Taken together, our findings contribute to a better understanding of the underlying mechanisms of circRNAs in GC progression. Furthermore, a robust prognostic signature is meaningful to facilitate individualized treatment for patients with GC.
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22
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Li C, Hou X, Yuan S, Zhang Y, Yuan W, Liu X, Li J, Wang Y, Guan Q, Zhou Y. High expression of TREM2 promotes EMT via the PI3K/AKT pathway in gastric cancer: bioinformatics analysis and experimental verification. J Cancer 2021; 12:3277-3290. [PMID: 33976737 PMCID: PMC8100818 DOI: 10.7150/jca.55077] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Accepted: 03/15/2021] [Indexed: 01/17/2023] Open
Abstract
Background: To date, the pathogenesis of gastric cancer (GC) remains unclear. We combined public database resources and bioinformatics analysis methods, explored some novel genes and verified the experiments to further understand the pathogenesis of GC and to provide a promising target for anti-tumor therapy. Methods: We downloaded the chip data related to GC from the Gene Expression Omnibus (GEO) database, extracted differentially expressed genes (DEGs), and then determined the key genes in the development of GC via PPI networks and model analysis. Functional annotation via GO and KEGG enrichment of DEGs was used to understand the latent roles of DEGs. The expression of the triggering receptor expressed on myeloid cells 2 (TREM2) gene in GC cell lines was verified via RT-PCR and western blotting. Moreover, the CCK-8, wound healing assay, and transwell migration and invasion assays were used to understand the changes in the proliferation, migration, and invasion abilities of GC cells after silencing TREM2. Western blotting verified the interaction between TREM2 and PI3K predict of the string website, as well as the effect of TREM2 on EMT. Finally, a lung metastasis model was used to explore the relationship between TREM2 and metastasis. Results: Our study identified 16 key genes, namely BGN, COL1A1, COL4A1, COL5A2, NOX4, SPARC, HEYL, SPP1, TIMP1, CTHRC1, TREM2, SFRP4, FBXO32, GPX3, KIF4A, and MMP9 genes associated with GC. The EMT-related pathway was the most significantly altered pathway. TREM2 expression was higher in GC cell lines and was remarkably associated with tumor invasion depth, TNM stage, histological grade, histological type, anatomic subdivision, and Helicobacter pylori state. Knockdown of TREM2 expression inhibited the proliferation, migration, and invasion of GC cells as well as the progression of EMT by PI3K/AKT signaling in vitro. In addition, lung metastasis were decreased in vivo. Conclusions: We identified some important genes associated with the progression of GC via public database analysis, explored and verified the effects of proto-oncogene TREM2 on EMT via the PI3K/AKT pathway. TREM2 may be a novel target in the GC therapy.
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Affiliation(s)
- Chunmei Li
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.,Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, China.,Department of Oncology, The First Hospital of Lanzhou University, Lanzhou, China
| | - Xiaoming Hou
- Department of Oncology, The First Hospital of Lanzhou University, Lanzhou, China
| | - Shuqiao Yuan
- Department of medical laboratory, The First Hospital of Lanzhou University, Lanzhou, China
| | - Yigan Zhang
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
| | - Wenzhen Yuan
- Department of Oncology Surgery, The First Hospital of Lanzhou University, Lanzhou, China
| | - Xiaoguang Liu
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.,Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, China.,Department of Rheumatology, The First Hospital of Lanzhou University, Lanzhou, China
| | - Juan Li
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.,Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, China.,Department of Gastroenterology, Gansu Provincial Hospital, Lanzhou, China
| | - Yuping Wang
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.,Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, China
| | - Quanlin Guan
- Department of Oncology Surgery, The First Hospital of Lanzhou University, Lanzhou, China
| | - Yongning Zhou
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.,Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, China
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23
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Liu Y, Hu X, Hu L, Xu C, Liang X. Let-7i-5p enhances cell proliferation, migration and invasion of ccRCC by targeting HABP4. BMC Urol 2021; 21:49. [PMID: 33775245 PMCID: PMC8005230 DOI: 10.1186/s12894-021-00820-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Accepted: 03/19/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Clear cell renal cell carcinoma (ccRCC) is one of the best-characterized and most pervasive renal cancers. The present study aimed to explore the effects and potential mechanisms of let-7i-5p in ccRCC cells. METHODS Using bioinformatics analyses, we investigated the expression of let-7i-5p in The Cancer Genome Atlas (TCGA) database and predicted biological functions and possible target genes of let-7i-5p in ccRCC cells. Cell proliferation assay, wound healing assay and transwell invasion assay were conducted to characterize the effects of let-7i-5p in ccRCC cells. To verify the interactions between let-7i-5p and HABP4, dual-luciferase reporter assay, quantitative real-time polymerase chain reaction, and western blotting were conducted. Rescue experiments were used to investigate the relationship between let-7i-5p and HABP4. RESULTS TCGA data analysis revealed that ccRCC tissues had significantly increased let-7i-5p expression, which was robustly associated with poor overall survival. Further verification showed that ccRCC cell proliferation, migration and invasion were inhibited by let-7i-5p inhibitor but enhanced by let-7i-5p mimics. Subsequently, HABP4 was predicted to be the target gene of let-7i-5p. TCGA data showed that ccRCC tissues had decreased expression of HABP4 and that HABP4 expression was negatively correlated with let-7i-5p. Further verification showed that downregulation of HABP4 expression promoted cell proliferation, migration and invasion. The dual-luciferase reporter gene assay suggested that the let-7i-5p/HABP4 axis was responsible for the development of ccRCC. CONCLUSION Our results provide evidence that let-7i-5p functions as a tumor promoter in ccRCC and facilitates cell proliferation, migration and invasion by targeting HABP4. These results clarify the pathogenesis of ccRCC and offer a potential target for its treatment.
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Affiliation(s)
- Yujie Liu
- Department of Geriatric Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China
| | - Xing Hu
- Department of General Practice, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China
| | - Liang Hu
- Department of Cardiovascular Surgery, The General Hospital of Western Theater Command, Chengdu, 610083, China
| | - Changjing Xu
- Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China
| | - Xuemei Liang
- Department of Geriatric Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
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24
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Wang C, Wallerman O, Arendt ML, Sundström E, Karlsson Å, Nordin J, Mäkeläinen S, Pielberg GR, Hanson J, Ohlsson Å, Saellström S, Rönnberg H, Ljungvall I, Häggström J, Bergström TF, Hedhammar Å, Meadows JRS, Lindblad-Toh K. A novel canine reference genome resolves genomic architecture and uncovers transcript complexity. Commun Biol 2021; 4:185. [PMID: 33568770 PMCID: PMC7875987 DOI: 10.1038/s42003-021-01698-x] [Citation(s) in RCA: 73] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Accepted: 12/17/2020] [Indexed: 12/13/2022] Open
Abstract
We present GSD_1.0, a high-quality domestic dog reference genome with chromosome length scaffolds and contiguity increased 55-fold over CanFam3.1. Annotation with generated and existing long and short read RNA-seq, miRNA-seq and ATAC-seq, revealed that 32.1% of lifted over CanFam3.1 gaps harboured previously hidden functional elements, including promoters, genes and miRNAs in GSD_1.0. A catalogue of canine "dark" regions was made to facilitate mapping rescue. Alignment in these regions is difficult, but we demonstrate that they harbour trait-associated variation. Key genomic regions were completed, including the Dog Leucocyte Antigen (DLA), T Cell Receptor (TCR) and 366 COSMIC cancer genes. 10x linked-read sequencing of 27 dogs (19 breeds) uncovered 22.1 million SNPs, indels and larger structural variants. Subsequent intersection with protein coding genes showed that 1.4% of these could directly influence gene products, and so provide a source of normal or aberrant phenotypic modifications.
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Affiliation(s)
- Chao Wang
- Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
| | - Ola Wallerman
- Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
| | - Maja-Louise Arendt
- Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
- Department of Veterinary Clinical Sciences, University of Copenhagen, Frederiksberg D, Denmark
| | - Elisabeth Sundström
- Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
| | - Åsa Karlsson
- Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
| | - Jessika Nordin
- Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
| | - Suvi Mäkeläinen
- Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
- Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden
| | - Gerli Rosengren Pielberg
- Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
| | - Jeanette Hanson
- Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden
| | - Åsa Ohlsson
- Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden
| | - Sara Saellström
- Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden
| | - Henrik Rönnberg
- Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden
| | - Ingrid Ljungvall
- Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden
| | - Jens Häggström
- Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden
| | - Tomas F Bergström
- Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden
| | - Åke Hedhammar
- Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden
| | - Jennifer R S Meadows
- Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
| | - Kerstin Lindblad-Toh
- Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
- Broad Institute of MIT and Harvard, Cambridge, MA, USA.
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25
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Yang Y, Li W, Wei B, Wu K, Liu D, Zhu D, Zhang C, Wen F, Fan Y, Zhao S. MicroRNA let-7i Inhibits Histone Lysine Demethylase KDM5B to Halt Esophageal Cancer Progression. MOLECULAR THERAPY. NUCLEIC ACIDS 2020; 22:846-861. [PMID: 33230480 PMCID: PMC7658493 DOI: 10.1016/j.omtn.2020.09.012] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Accepted: 09/11/2020] [Indexed: 11/25/2022]
Abstract
Recent studies have suggested that microRNA let-7i is a tumor suppressor in human cancers, including esophageal cancer, but its underlying mechanism is not yet fully understood. We investigated the role and mechanisms of let-7i in the progression of esophageal cancer. We first showed that let-7i was downregulated in esophageal cancer tissues and cells and then linked its low expression to cancer progression. Bioinformatic analysis predicted KDM5B as a target gene of let-7i, which was confirmed by a dual-luciferase reporter assay. Loss- and gain-of function approaches were adopted to examine the interactions of let-7i, KDM5B, SOX17, and GREB1 in vitro and in vivo. Overexpression of let-7i suppressed esophageal cancer cell proliferation and invasion and promoted apoptosis. Mechanistic investigation showed that let-7i targeted and inhibited KDM5B expression, whereas KDM5B enhanced H3K4me3 at the SOX17 promoter region. Overexpression of let-7i suppressed the expression of GREB1 in esophageal cancer cells by regulating the KDM5B/SOX17 axis in vivo and in vitro. Taken together, our findings reveal the tumor-suppressive properties of let-7i in esophageal cancer in association with an apparent KDM5B-dependent SOX17/GREB1 axis. This study offers a potential prognostic marker and therapeutic target for esophageal cancer.
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Affiliation(s)
- Yang Yang
- Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450015, P.R. China
| | - Wenhua Li
- Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450015, P.R. China
| | - Bochong Wei
- Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450015, P.R. China
| | - Kai Wu
- Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450015, P.R. China
| | - Donglei Liu
- Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450015, P.R. China
| | - Dengyan Zhu
- Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450015, P.R. China
| | - Chunyang Zhang
- Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450015, P.R. China
| | - Fengbiao Wen
- Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450015, P.R. China
| | - Yuxia Fan
- Department of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450015, P.R. China
| | - Song Zhao
- Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450015, P.R. China
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26
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Xie S, Chang Y, Jin H, Yang F, Xu Y, Yan X, Lin A, Shu Q, Zhou T. Non-coding RNAs in gastric cancer. Cancer Lett 2020; 493:55-70. [PMID: 32712234 DOI: 10.1016/j.canlet.2020.06.022] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 06/19/2020] [Accepted: 06/28/2020] [Indexed: 12/11/2022]
Abstract
Non-coding RNAs (ncRNAs) are functional RNA molecules that play crucial regulatory roles in many fundamental biological processes. The dysregulation of ncRNAs is significantly associated with the progression of human cancers, including gastric cancer. In this review, we have summarized the oncogenic or tumor-suppressive roles and the regulatory mechanisms of lncRNAs, miRNAs, circRNAs and piRNAs, and have discussed their potential as biomarkers or therapeutic targets in gastric cancer.
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Affiliation(s)
- Shanshan Xie
- The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, China; Department of Cell Biology and Cancer Institute of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China
| | - Yongxia Chang
- Department of Cell Biology and Cancer Institute of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China; Cancer Center, Zhejiang University, Hangzhou, 310058, China
| | - Hao Jin
- Department of Cell Biology and Cancer Institute of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China; Cancer Center, Zhejiang University, Hangzhou, 310058, China
| | - Feng Yang
- Department of Cell Biology and Cancer Institute of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China; Cancer Center, Zhejiang University, Hangzhou, 310058, China
| | - Yanjun Xu
- Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, 310022, China
| | - Xiaoyi Yan
- Cancer Center, Zhejiang University, Hangzhou, 310058, China
| | - Aifu Lin
- MOE Laboratory of Biosystem Homeostasis and Protection, College of Life Sciences, Zhejiang University, Hangzhou, 310058, China.
| | - Qiang Shu
- The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, China.
| | - Tianhua Zhou
- Department of Cell Biology and Cancer Institute of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China; Cancer Center, Zhejiang University, Hangzhou, 310058, China; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
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27
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Yang B, Zhang M, Luo T. Identification of Potential Core Genes Associated With the Progression of Stomach Adenocarcinoma Using Bioinformatic Analysis. Front Genet 2020; 11:517362. [PMID: 33193601 PMCID: PMC7642829 DOI: 10.3389/fgene.2020.517362] [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: 12/04/2019] [Accepted: 09/28/2020] [Indexed: 12/24/2022] Open
Abstract
Purpose Stomach adenocarcinoma (STAD) is one of the most frequently diagnosed cancer in the world with both high mortality and high metastatic capacity. Therefore, the present study aimed to investigate novel therapeutic targets and prognostic biomarkers that can be used for STAD treatment. Materials and Methods We acquired four original gene chip profiles, namely GSE13911, GSE19826, GSE54129, and GSE65801 from the Gene Expression Omnibus (GEO). The datasets included a total of 114 STAD tissues and 110 adjacent normal tissues. The GEO2R online tool and Venn diagram software were used to discriminate differentially expressed genes (DEGs). Gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) enriched pathways were also performed for annotation and visualization with DEGs. The STRING online database was used to identify the functional interactions of DEGs. Subsequently, we selected the most significant DEGs to construct the protein-protein interaction (PPI) network and to reveal the core genes involved. Finally, the Kaplan-Meier Plotter online database and Gene Expression Profiling Interactive Analysis (GEPIA) were used to analyze the prognostic information of the core DEGs. Results A total of 114 DEGs (35 upregulated and 79 downregulated) were identified, which were abnormally expressed in the GEO datasets. GO analysis demonstrated that the majority of the upregulated DEGs were significantly enriched in collagen trimer, cell adhesion, and identical protein binding. The downregulated DEGs were involved in extracellular space, digestion, and inward rectifier potassium channel activity. Signaling pathway analysis indicated that upregulated DEGs were mainly enriched in receptor interaction, whereas downregulated DEGs were involved in gastric acid secretion. A total of 80 DEGs were screened into the PPI network complex, and one of the most important modules with a high degree was detected. Furthermore, 10 core genes were identified, namely COL1A1, COL1A2, FN1, COL5A2, BGN, COL6A3, COL12A1, THBS2, CDH11, and SERPINH1. Finally, the results of the prognostic information further demonstrated that all 10 core genes exhibited significantly higher expression in STAD tissues compared with that noted in normal tissues. Conclusion The multiple molecular mechanisms of these novel core genes in STAD are worthy of further investigation and may reveal novel therapeutic targets and biomarkers for STAD treatment.
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Affiliation(s)
- Biao Yang
- Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Meijing Zhang
- Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Tianhang Luo
- Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China
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28
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Zu F, Han H, Sheng W, Sun J, Zang H, Liang Y, Liu Q. Identification of a competing endogenous RNA axis related to gastric cancer. Aging (Albany NY) 2020; 12:20540-20560. [PMID: 33080572 PMCID: PMC7655175 DOI: 10.18632/aging.103926] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 07/30/2020] [Indexed: 01/10/2023]
Abstract
Competing endogenous RNA (ceRNA) pathways play pivotal roles in the formation and progression of gastric cancer (GC). Employing multi-omics analysis, we sought to identify a ceRNA network associated with GC progression. We analyzed3Gene Expression Omnibus datasets as well as data from The Cancer Genome Atlas to identify genes that were differentially expressed in GC tissues. A total of 84 upregulated genes and 106 downregulated genes were found. Enrichment analysis indicated that some pathways were strongly linked with tumor formation and progression. We also screened hub genes to establish a lncRNA-miRNA-mRNA network. We ultimately identified 8 hub genes, 6 key miRNAs and 4 key lncRNAs that interact within a common ceRNA network. Correlation analysis and in vitro experiments were conducted to verify the regulatory effect of the ceRNA network in GC. A knockdown assay confirmed that the DLGAP1-AS1/miR-203a-3p/THBS2 axis is a ceRNA network involved in GC progression. In this study, we elucidated the role of the DLGAP1-AS1/miR-203a-3p/THBS2 ceRNA network in the progression of GC. These molecules maybe evaluated as therapeutic targets and prognostic biomarkers for GC.
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Affiliation(s)
- Fuqiang Zu
- Department of General Surgery, The People’s Hospital of China Medical University, Shenyang 110016, Liaoning, China
| | - Hezhou Han
- Central Laboratory of General Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, China
| | - Weiwei Sheng
- Department of Gastrointestinal and Hernia Surgery, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning, China
| | - Jian Sun
- Department of Gastrointestinal and Hernia Surgery, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning, China
| | - Hui Zang
- Department of General Surgery, The People’s Hospital of China Medical University, Shenyang 110016, Liaoning, China
| | - Yu Liang
- Department of General Surgery, The People’s Hospital of China Medical University, Shenyang 110016, Liaoning, China
| | - Qingfeng Liu
- Department of General Surgery, The People’s Hospital of China Medical University, Shenyang 110016, Liaoning, China
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An Q, Liu T, Wang MY, Yang YJ, Zhang ZD, Lin ZJ, Yang B. circKRT7-miR-29a-3p-COL1A1 Axis Promotes Ovarian Cancer Cell Progression. Onco Targets Ther 2020; 13:8963-8976. [PMID: 32982288 PMCID: PMC7490051 DOI: 10.2147/ott.s259033] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Accepted: 07/28/2020] [Indexed: 12/12/2022] Open
Abstract
Background Circular RNA (circRNA) has emerged as an important regulator in the progression of human diseases. However, the role of circRNAs in ovarian cancer remains largely unknown. Materials and Methods DNA sequencing and PCR were used to identify the existence and expression of circKRT7. The targeting relationship between circKRT7/miR-29a-3p and miR-29a-3p/COL1A1 was verified by fluorescence reporter assay. In vitro, colony formation, transwell and wound healing assay were used to detect the effects of circKRT7 and miR-29a-3p on the proliferation, migration and invasion ability of ovarian cancer cells. In vivo, xenograft tumor model was performed to validate the role of circKRT7 and miR-29a-3p in tumor growth. Results We found that circKRT7 can promote the proliferation and metastasis of ovarian cancer cells by absorbing miR-29a-3p, which leads to the up-regulation of COL1A1. In vitro, knock-down of circKRT7 can inhibit the migration and invasion of ovarian cancer cells. This effect of circKRT7 is achieved by adsorbing miR-29a-3p and subsequently COL1A1 release. In vivo experiments, the reduction of circKRT7 expression can also slow tumor growth, and this inhibition was partly counteracted after miR-29a-3p repression. Conclusion Overall, circKRT7 promotes EMT-related cell progression by absorbing miR-29a-3p in ovarian cancer. This suggests the crucial role of circular RNA in the malignant evolution in cancer.
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Affiliation(s)
- Qiang An
- Department of Gynecology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, People's Republic of China
| | - Ting Liu
- Department of Gynecology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, People's Republic of China
| | - Ming-Yang Wang
- Department of Gynecology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, People's Republic of China
| | - Yu-Jia Yang
- Department of Gynecology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, People's Republic of China
| | - Zhen-Dong Zhang
- Department of Gynecology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, People's Republic of China
| | - Zhen-Jiang Lin
- Department of Gynecology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, People's Republic of China
| | - Bing Yang
- Department of Gynecology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, People's Republic of China
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A novel ceRNA axis involves in regulating immune infiltrates and macrophage polarization in gastric cancer. Int Immunopharmacol 2020; 87:106845. [PMID: 32763781 DOI: 10.1016/j.intimp.2020.106845] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Revised: 07/05/2020] [Accepted: 07/26/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND Increasing evidence suggests that the lncRNA-miRNA-mRNA regulatory network is highly correlated with gastric cancer (GC) development. However, a prognosis-associated lncRNA-miRNA-mRNA network remains to be identified in GC. METHODS Differentially expressed genes (DEGs) were screened by integrating 6 microarray datasets using the RRA method. Hub genes were identified by analysing their degrees in a PPI (protein-protein interaction) network. Upstream miRNAs and lncRNAs of hub genes were predicted by miRTarBase and miRNet, respectively. Key genes, miRNAs and lncRNAs were identified by evaluating their expression and prognosis in GEPIA and Kaplan-Meier plotter, respectively. A key lncRNA-miRNA-mRNA network was constructed in Cytoscape, and the correlations were analysed in the ENCORI database. We also evaluated the mRNA expression of ceRNA axes in the TIMER and Oncomine databases and their correlation with prognosis in GC patients with different clinical features using Kaplan-Meier plotter. In addition, correlations between mRNA and immune infiltrating cells in GC were investigated by the TIMER database. Finally, several experiments were conducted to verify our analyses. RESULTS Forty-two upregulated and 86 downregulated DEGs were obtained from the "RRA" integrated analysis. Eight of the 20 hub genes were identified as key genes by analysing their expression and prognosis. Seventeen miRNAs were predicted to target key genes, and low expression of 4 miRNAs suggested poor outcome in GC. Furthermore, 155 lncRNAs were predicted to target 4 key miRNAs, and only 5 lncRNAs were highly expressed, suggesting poor outcomes in patients with GC. Then, the H19-miR-29a-3p-COL1A2 axis was constructed by correlation analysis. In addition, COL1A2 was positively correlated with lymphatic metastasis, immune infiltrating cell levels, markers of monocytes, tumour-associated macrophages (TAMs), and M2 macrophages but not M1 macrophages in GC. The experimental results revealed that the H19-miR-29a-3p-COL1A2 axis may promote macrophage polarization from M1 to M2 in GC. CONCLUSIONS A novel lncRNA-miRNA-mRNA axis was identified and may be involved in regulating immune cell infiltration and macrophage polarization, which may provide new treatment strategies for GC.
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Huang J, Wen F, Huang W, Bai Y, Lu X, Shu P. Identification of hub genes and discovery of promising compounds in gastric cancer based on bioinformatics analysis. Biomark Med 2020; 14:1069-1084. [PMID: 32969243 DOI: 10.2217/bmm-2019-0608] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Aim: To explore the mechanism of gastric carcinogenesis by mining potential hub genes and to search for promising small-molecular compounds for gastric cancer (GC). Materials & methods: The microarray datasets were downloaded from Gene Expression Omnibus database and the genes and compounds were analyzed by bioinformatics-related tools and software. Results: Six hub genes (MKI67, PLK1, COL1A1, TPX2, COL1A2 and SPP1) related to the prognosis of GC were confirmed to be upregulated in GC and their high expression was correlated with poor overall survival rate in GC patients. In addition, eight candidate compounds with potential anti-GC activity were identified, among which resveratrol was closely correlated with six hub genes. Conclusion: Six hub genes identified in the present study may contribute to a more comprehensive understanding of the mechanism of gastric carcinogenesis and the predicted potential of resveratrol may provide valuable clues for the future development of targeted anti-GC inhibitors.
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Affiliation(s)
- Jiani Huang
- Nanjing University of Chinese Medicine, Nanjing210029, Jiangsu Province, China
- College of Traditional ChineseMedicine, College of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Fang Wen
- Nanjing University of Chinese Medicine, Nanjing210029, Jiangsu Province, China
- Department of Oncology, Affiliated Hospital ofNanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
- Department of Oncology, Jiangsu Province Hospitalof Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Wenjie Huang
- Nanjing University of Chinese Medicine, Nanjing210029, Jiangsu Province, China
- Department of Oncology, Affiliated Hospital ofNanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
- Department of Oncology, Jiangsu Province Hospitalof Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Yingfeng Bai
- Nanjing University of Chinese Medicine, Nanjing210029, Jiangsu Province, China
- College of Traditional ChineseMedicine, College of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Xiaona Lu
- Nanjing University of Chinese Medicine, Nanjing210029, Jiangsu Province, China
- Department of Oncology, Affiliated Hospital ofNanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
- Department of Oncology, Jiangsu Province Hospitalof Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Peng Shu
- Nanjing University of Chinese Medicine, Nanjing210029, Jiangsu Province, China
- Department of Oncology, Affiliated Hospital ofNanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
- Department of Oncology, Jiangsu Province Hospitalof Chinese Medicine, Nanjing 210029, Jiangsu Province, China
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Chen Y, Chen W, Dai X, Zhang C, Zhang Q, Lu J. Identification of the collagen family as prognostic biomarkers and immune-associated targets in gastric cancer. Int Immunopharmacol 2020; 87:106798. [PMID: 32693357 DOI: 10.1016/j.intimp.2020.106798] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 07/03/2020] [Accepted: 07/07/2020] [Indexed: 12/29/2022]
Abstract
BACKGROUND Gastric cancer has extremely high morbidity and mortality. Currently, it is lack of effective biomarkers and therapeutic targets for guiding clinical treatment. In this study, we aimed to identify novel biomarkers and therapeutic targets for gastric cancer. METHODS Differentially expressed genes (DEGs) between gastric cancer and normal tissues were obtained from Gene Expression Omnibus (GEO). Core genes were identified by constructing protein-protein interaction network of DEGs. The expression of core genes was verified in Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN and clinical samples. Further, the mutation, DNA methylation, prognostic value, and immune infiltration of core genes were validated by cBioPortal, MethSurv, Kaplan-Meier plotter, and Tumor Immune Estimation Resource (TIMER) databases. Additionally, drug response analysis was performed by Cancer Therapy Response Portal (CTRP). RESULTS A total of seven collagen family members were identified as core genes among upregulated genes. And copy number amplification may be involved in the upregulation of COL1A1 and COL1A2. Importantly, the collagen family was associated with the poor prognosis of patients with metastasis. Among them, COL1A1 had a higher hazard ratio (HR) for overall survival than other members (HR = 2.33). The correlation between DNA methylation levels at CpG sites of collagen family members and the prognosis was verified in gastric cancer. Besides, collagen family expression was positively correlated with macrophages infiltration and the expression of M2 macrophages markers. Further, collagen expression was related to the sensitivity and resistance of gastric cancer cell lines to certain drugs. CONCLUSIONS The collagen family, especially COL1A1, COL1A2, and COL12A1, may act as potential prognostic biomarkers and immune-associated therapeutic targets in gastric cancer.
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Affiliation(s)
- Yihuan Chen
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan Province 450001, PR China
| | - Wei Chen
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan Province 450001, PR China
| | - Xiaoshuo Dai
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan Province 450001, PR China
| | - Chengjuan Zhang
- Department of Pathology, Henan Cancer Hospital, Zhengzhou University, Zhengzhou, Henan Province 450003, PR China
| | - Qiushuang Zhang
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan Province 450001, PR China
| | - Jing Lu
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan Province 450001, PR China; Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, Henan Province 450001, PR China; State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province 450052, PR China.
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Microenvironment remodeled by tumor and stromal cells elevates fibroblast-derived COL1A1 and facilitates ovarian cancer metastasis. Exp Cell Res 2020; 394:112153. [PMID: 32589888 DOI: 10.1016/j.yexcr.2020.112153] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2020] [Revised: 06/08/2020] [Accepted: 06/21/2020] [Indexed: 01/25/2023]
Abstract
Wide peritoneal metastasis is the cause of the highest lethality of ovarian cancer in gynecologic malignancies. Ascites play a key role in ovarian cancer metastasis, but involved mechanism is uncertain. Here, we performed a quantitative proteomics of ascites, and found that collagen type I alpha 1 (COL1A1) was notably elevated in ascites from epithelial ovarian cancer patients compared to normal peritoneal fluids, and verified that elevated COL1A1 was mainly originated from fibroblasts. COL1A1 promoted migration and invasion of ovarian cancer cells, but such effects were partially eliminated by COL1A1 antibodies. Intraperitoneally injected COL1A1 accelerated intraperitoneal metastasis of ovarian cancer xenograft in NOD/SCID mice. Further, COL1A1 activated downstream AKT phosphorylation by binding to membrane surface receptor integrin β1 (ITGB1). Knockdown or blockage of ITGB1 reversed COL1A1 enhanced migration and invasion in ovarian cancer cells. Conversely, ovarian cancer ascites and fibrinogen promoted fibroblasts to secrete COL1A1. Elevated fibrinogen in ascites might be associated with increased vascular permeability induced by ovarian cancer. Our findings suggest that microenvironment remodeled by tumor cells and stromal cells promotes fibroblasts to secrete COL1A1 and facilitates the metastasis of ovarian cancer, which may provide a new approach for ovarian cancer therapeutics.
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Chen PY, Li XD, Ma WN, Li H, Li MM, Yang XY, Li SY. Comprehensive Transcriptomic Analysis and Experimental Validation Identify lncRNA HOXA-AS2/miR-184/COL6A2 as the Critical ceRNA Regulation Involved in Low-Grade Glioma Recurrence. Onco Targets Ther 2020; 13:4999-5016. [PMID: 32581558 PMCID: PMC7276213 DOI: 10.2147/ott.s245896] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Accepted: 04/16/2020] [Indexed: 12/18/2022] Open
Abstract
Purpose The recurrence and metastasis of glioma are closely related to complex regulatory networks among protein-coding genes, lncRNAs and microRNAs. The aim of this study was to investigate core genes, lncRNAs, miRNAs and critical ceRNA regulatory mechanisms, which are involved in lower-grade glioma (LGG) recurrence. Materials and Methods We employed multiple datasets from Chinese Glioma Genome Atlas (CGGA) database and The Cancer Genome Atlas (TCGA) to perform comprehensive transcriptomic analysis. Further in vitro experiments including cell proliferation assay, luciferase reporter assay, and Western blot were performed to validate our results. Results Recurrent LGG and glioblastoma (GBM) showed different transcriptome characteristics with less overlap of differentially expressed protein-coding genes (DEPs), lncRNAs (DELs) and miRNAs (DEMs) compared with primary samples. There were no overlapping gene in ontology (GO) terms related to GBM recurrence in the TCGA and CGGA databases, but there were overlaps associated with LGG recurrence. GO analysis and protein–protein interaction (PPI) network analysis identified three core genes: TIMP1, COL1A1 and COL6A2. By hierarchical cluster analysis of them, LGGs could be clustered as Low_risk and High_risk group. The High_risk group with high expression of TIMP1, COL1A1, and COL6A2 showed worse prognosis. By coexpression networks analysis, competing endogenous RNA (ceRNA) network analysis, cell proliferation assay and luciferase reporter assay, we confirmed that lncRNA HOXA-AS2 functioned as a ceRNA for miR-184 to regulate expression of COL6A2, which induced cell proliferation of low-grade glioma. Conclusion In this study, we revealed a 3-hub protein-coding gene signature to improve prognostic prediction in LGG, and identified a critical ceRNA regulation involved in LGG recurrence.
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Affiliation(s)
- Peng-Yu Chen
- Department of Neurosurgery, Shengjing Hospital Affiliated to China Medical University, Shenyang, People's Republic of China
| | - Xiao-Dong Li
- Department of Neurosurgery, Shengjing Hospital Affiliated to China Medical University, Shenyang, People's Republic of China
| | - Wei-Ning Ma
- Department of Neurosurgery, Shengjing Hospital Affiliated to China Medical University, Shenyang, People's Republic of China
| | - Han Li
- Department of Neurosurgery, Shengjing Hospital Affiliated to China Medical University, Shenyang, People's Republic of China
| | - Miao-Miao Li
- Department of Neurosurgery, Shengjing Hospital Affiliated to China Medical University, Shenyang, People's Republic of China
| | - Xin-Yu Yang
- Department of Neurosurgery, Shengjing Hospital Affiliated to China Medical University, Shenyang, People's Republic of China
| | - Shao-Yi Li
- Department of Neurosurgery, Shengjing Hospital Affiliated to China Medical University, Shenyang, People's Republic of China
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Li Z, Liu Z, Shao Z, Li C, Li Y, Liu Q, Zhang Y, Tan B, Liu Y. Identifying multiple collagen gene family members as potential gastric cancer biomarkers using integrated bioinformatics analysis. PeerJ 2020; 8:e9123. [PMID: 32509452 PMCID: PMC7255341 DOI: 10.7717/peerj.9123] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Accepted: 04/13/2020] [Indexed: 12/24/2022] Open
Abstract
Background Gastric cancer is one of the most common malignant cancers worldwide. Despite substantial developments in therapeutic strategies, the five-year survival rate remains low. Therefore, novel biomarkers and therapeutic targets involved in the progression of gastric tumors need to be identified. Methods We obtained the mRNA microarray datasets GSE65801, GSE54129 and GSE79973 from the Gene Expression Omnibus database to acquire differentially expressed genes (DEGs). We used the Database for Annotation, Visualization, and Integrated Discovery (DAVID) to analyze DEG pathways and functions, and the Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape to obtain the protein-protein interaction (PPI) network. Next, we validated the hub gene expression levels using the Oncomine database and Gene Expression Profiling Interactive Analysis (GEPIA), and conducted stage expression and survival analysis. Results From the three microarray datasets, we identified nine major hub genes: COL1A1, COL1A2, COL3A1, COL5A2, COL4A1, FN1, COL5A1, COL4A2, and COL6A3. Conclusion Our study identified COL1A1 and COL1A2 as potential gastric cancer prognostic biomarkers.
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Affiliation(s)
- Zhaoxing Li
- Department of General Surgery, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, China
| | - Zhao Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing, China
| | - Zhiting Shao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Institute, Beijing, China
| | - Chuang Li
- The Second Hospital of Shijiazhuang, Shijiazhuang, China
| | - Yong Li
- Department of General Surgery, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, China
| | - Qingwei Liu
- Department of General Surgery, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, China
| | | | - Bibo Tan
- Department of General Surgery, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yu Liu
- Department of General Surgery, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, China
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Qi M, Yu B, Yu H, Li F. Integrated analysis of a ceRNA network reveals potential prognostic lncRNAs in gastric cancer. Cancer Med 2020; 9:1798-1817. [PMID: 31923354 PMCID: PMC7050084 DOI: 10.1002/cam4.2760] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Revised: 11/18/2019] [Accepted: 11/21/2019] [Indexed: 01/17/2023] Open
Abstract
Long noncoding RNAs (lncRNAs) have important biological functions as competing endogenous RNAs (ceRNAs) in tumors, yet the functions and regulatory mechanisms of lncRNA-related ceRNAs in gastric cancer have not been fully elucidated. In this study, we constructed a lncRNA-miRNA-mRNA ceRNA network and identified potential lncRNA biomarkers in gastric cancer. Basing on the RNA profiles downloaded from The Cancer Genome Atlas (TCGA) platform, the gastric cancer-specific differentially expressed lncRNAs, miRNAs, and mRNAs were screened for constructing a ceRNA network using bioinformatic tools. The enrichment analysis of the biological processes in Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathways was performed on the ceRNA-related DEmRNAs. According to the modularization of protein-protein interaction (PPI) network, we extracted a ceRNA subnetwork and analyzed the correlation between the expression of the lncRNAs involved and specific clinical features of patients. Next, the expression of highly up-regulated in liver cancer (HULC) and RP11-314B1.2 showed significant changes in several pathological processes involved in gastric cancer, and nine lncRNAs were found to be correlated with the overall survival of patients with gastric cancer. Through the univariate and multivariate Cox regression analyses, two lncRNAs (LINC00106 and RP11-999E24.3) were identified and utilized to establish a risk score model for assessing the prognosis of patients. The analysis results were also partially verified using quantitative real-time PCR. The findings from this study indicate that HULC, RP11-314B1.2, LINC00106, and RP11-999E24.3 could be considered as potential therapeutic targets or prognostic biomarkers in gastric cancer, and provide a new perspective for cancer pathogenesis research.
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Affiliation(s)
- Mingran Qi
- Department of PathogenobiologyThe Key Laboratory of ZoonosisChinese Ministry of EducationCollege of Basic MedicineJilin UniversityChangchunJilinChina
| | - Bingxin Yu
- Department of UltrasoundChina‐Japan Union Hospital of Jilin UniversityChangchunJilinChina
| | - Huiyuan Yu
- School of Public HealthJilin UniversityChangchunJilinChina
| | - Fan Li
- Department of PathogenobiologyThe Key Laboratory of ZoonosisChinese Ministry of EducationCollege of Basic MedicineJilin UniversityChangchunJilinChina
- The Key Laboratory for Bionics EngineeringMinistry of EducationJilin UniversityChinaChangchunJilinChina
- Engineering Research Center for Medical Biomaterials of Jilin ProvinceJilin UniversityChangchunJilinChina
- Key Laboratory for Biomedical Materials of Jilin ProvinceJilin UniversityChangchunJilinChina
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central AsiaXinjiangChina
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Guo C, Shao T, Wei D, Li C, Liu F, Li M, Gao Z, Bao G. Bioinformatic Identification of Potential Hub Genes in Muscle-Invasive Bladder Urothelial Carcinoma. Cell Transplant 2020; 29:963689720965178. [PMID: 33035117 PMCID: PMC7784563 DOI: 10.1177/0963689720965178] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 06/15/2020] [Accepted: 09/20/2020] [Indexed: 11/30/2022] Open
Abstract
Despite aggressive treatment approaches, muscle-invasive bladder urothelial carcinoma (MIBC) patients still have a 50% chance of developing general incurable metastases. Therefore, there is an urgent need for candidate markers to enhance diagnosis and generate effective treatments for this disease. We evaluated four mRNA microarray datasets to find differences between non-MIBC (NMIBC) and MIBC tissues. Through a gene expression profile analysis via the Gene Expression Omnibus database, we identified 56 differentially expressed genes (DEGs). Enrichment analysis of gene ontology, Kyoto Encyclopedia of Genes and Genomes, and Reactome pathways revealed the interactions between these DEGs. Next, we established a protein-protein interaction network to determine the interrelationship between the DEGs and selected 10 hub genes accordingly. Bladder urothelial carcinoma (BLCA) patients with COL1A2, COL5A1, and COL5A2 alterations showed poor disease-free survival rates, while BLCA patients with COL1A1 and LUM alterations showed poor overall survival rates. Oncomine analysis of MIBC versus NMIBC tissues showed that COL1A1, COL5A2, COL1A2, and COL3A1 were consistently among the top 20 overexpressed genes in different studies. Using the TCGAportal, we noted that the high expression of each of the four genes led to shorter BLCA patient overall survival. It was evident that BLCA patients with an elevated high combined gene expression had significantly shorter overall survival and relapse-free survival than those with low combined gene expression using PROGgeneV2. Using Gene Expression Profiling Interactive Analysis, we noted that COL1A1, COL1A2, COL3A1, and COL5A2 were positively correlated with each other in BLCA. These genes are considered as clinically relevant genes, suggesting that they may play an important role in the carcinogenesis, development, invasion, and metastasis of MIBC. However, considering we adopted a bioinformatic approach, more research is crucial to confirm our results. Nonetheless, our findings may have important prospective clinical implementations.
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Affiliation(s)
- Changgang Guo
- Department of Urology, Affiliated Hospital of Chifeng University, Chifeng, China
- Urology Research Center, Chifeng University, Chifeng, China
| | - Ting Shao
- Department of Gynecology, Affiliated Hospital of Chifeng University, Chifeng, China
| | - Dadong Wei
- Department of Urology, Affiliated Hospital of Chifeng University, Chifeng, China
| | - Chunsheng Li
- Department of Urology, Affiliated Hospital of Chifeng University, Chifeng, China
- Urology Research Center, Chifeng University, Chifeng, China
| | - Fengjun Liu
- Department of Urology, Affiliated Hospital of Chifeng University, Chifeng, China
| | - Minghui Li
- Department of Urology, Affiliated Hospital of Chifeng University, Chifeng, China
| | - Zhiming Gao
- Department of Urology, Affiliated Hospital of Chifeng University, Chifeng, China
- Urology Research Center, Chifeng University, Chifeng, China
| | - Guochang Bao
- Department of Urology, Affiliated Hospital of Chifeng University, Chifeng, China
- Urology Research Center, Chifeng University, Chifeng, China
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Wei S, Chen J, Huang Y, Sun Q, Wang H, Liang X, Hu Z, Li X. Identification of hub genes and construction of transcriptional regulatory network for the progression of colon adenocarcinoma hub genes and TF regulatory network of colon adenocarcinoma. J Cell Physiol 2019; 235:2037-2048. [PMID: 31612481 PMCID: PMC6916361 DOI: 10.1002/jcp.29067] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Accepted: 06/20/2019] [Indexed: 12/13/2022]
Abstract
The aim of this study was to identify key genes related to the progression of colon adenocarcinoma (COAD), and to investigate the regulatory network of hub genes and transcription factors (TFs). Dataset GSE20916 including 44 normal colon, 55 adenoma, and 36 adenocarcinoma tissue samples was used to construct co‐expression networks via weighted gene co‐expression network. Gene Ontology annotation and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis for the objective module were performed using the online Database for Annotation, Visualization and Integrated Discovery. Hub genes were identified by taking the intersection of differentially expressed genes between dataset GSE20916 and GSE39582 and validated using The Cancer Genome Atlas (TCGA) database. The correlations between microRNA (miRNA) and hub genes were analyzed using the online website StarBase. Cytoscape was used to establish a regulatory network of TF‐miRNA‐target gene. We found that the orange module was a key module related to the tumor progression in COAD. In datasets GSE20916 and GSE39582, a total of eight genes (BGN, SULF1, COL1A1, FAP, THBS2, CTHRC1, COL5A2, and COL1A2) were selected, which were closely related with patients’ survivals in TCGA database and dataset GSE20916. COAD patients with higher expressions of each hub gene had a worse prognosis than those with lower expressions. A regulatory network of TF‐miRNA‐target gene with 144 TFs, 26 miRNAs, and 7 hub genes was established, including model KLF11‐miR149‐BGN, TCEAL6‐miR29B2‐COL1A1, and TCEAL6‐miR29B2‐COL1A2. In conclusion, during the progression of COAD, eight core genes (BGN, SULF1, COL1A1, FAP, THBS2, CTHRC1, COL5A2, and COL1A2) play vital roles. Regulatory networks of TF‐miRNA‐target gene can help to understand the disease progression and optimize treatment strategy.
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Affiliation(s)
- Shuxun Wei
- Department of General Surgery, Changzheng Hospital, The Second Military Medical University, Shanghai, China
| | - Jinshui Chen
- Department of General Surgery, Changzheng Hospital, The Second Military Medical University, Shanghai, China
| | - Yu Huang
- Department of General Surgery, Changzheng Hospital, The Second Military Medical University, Shanghai, China
| | - Qiang Sun
- Department of General Surgery, Changzheng Hospital, The Second Military Medical University, Shanghai, China
| | - Haolu Wang
- The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, Queensland, Australia
| | - Xiaowen Liang
- The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, Queensland, Australia
| | - Zhiqian Hu
- Department of General Surgery, Changzheng Hospital, The Second Military Medical University, Shanghai, China
| | - Xinxing Li
- Department of General Surgery, Changzheng Hospital, The Second Military Medical University, Shanghai, China
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Li BG, Wu WJ, Zheng HC, Yang HF, Zuo YX, Cui XP. Long noncoding RNA GAS5 silencing inhibits the expression of KCNQ3 by sponging miR-135a-5p to prevent the progression of epilepsy. Kaohsiung J Med Sci 2019; 35:527-534. [PMID: 31373759 DOI: 10.1002/kjm2.12102] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Accepted: 06/03/2019] [Indexed: 02/06/2023] Open
Abstract
Epilepsy is one of the most common neurological disorders in humans. Recently, long noncoding RNAs (lncRNAs) have been reported to be important players in neurological diseases. Herein, this study aimed to examine the effect of lncRNA GAS5 on the occurrence of epilepsy in rat and cell models of epileptic seizure. The expression of lncRNA GAS5 was measured in the established rat and cell models. The binding sites between lncRNA GAS5 and miR-135a-5p, as well as those between miR-135a-5p and 3' untranslated region of KCNQ3 were predicted by miRDB and Targetscan, separately, followed by verification using dual-luciferase reporter gene assay. The expression of miR-135a-5p was measured in response to the overexpression of lncRNA GAS5. The mRNA and protein levels of KCNQ3 were examined in response to overexpression of miR-135a-5p. Next, the latency of epilepsy and frequency of epileptic seizures were assessed in rats injected with Lv-shGAS5 and Lv-miR-135a-5p in epileptic seizure model. In the rat and cell models, lncRNA GAS5 was highly expressed when epileptic seizure was induced. The expression of miR-135a-5p was decreased by overexpression of lncRNA GAS5. Meanwhile, the mRNA and protein levels of KCNQ3 were decreased in response to knockdown of miR-135a-5p. After the treatment of Lv-shGAS5 and Lv-miR-135a-5p, the average latent period of epilepsy was prolonged and the frequency of seizures was decreased. The key findings of the present study provide evidence emphasizing that lncRNA GAS5 functions as a competitive endogenous RNA of miR-135a-5p to increase expression of KCNQ3, and lncRNA GAS5 silencing inhibited the occurrence and progression of epilepsy.
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Affiliation(s)
- Bao-Guang Li
- Department of Neurology, Children's Hospital of Hebei Province, Shijiazhuang, Hebei, China
| | - Wen-Juan Wu
- Department of Neurology, Children's Hospital of Hebei Province, Shijiazhuang, Hebei, China
| | - Hua-Cheng Zheng
- Department of Neurology, Children's Hospital of Hebei Province, Shijiazhuang, Hebei, China
| | - Hua-Fang Yang
- Department of Neurology, Children's Hospital of Hebei Province, Shijiazhuang, Hebei, China
| | - Yue-Xian Zuo
- Department of Neurology, Children's Hospital of Hebei Province, Shijiazhuang, Hebei, China
| | - Xiao-Pu Cui
- Department of Neurology, Children's Hospital of Hebei Province, Shijiazhuang, Hebei, China
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Qin MM, Chai X, Huang HB, Feng G, Li XN, Zhang J, Zheng R, Liu XC, Pu C. let-7i inhibits proliferation and migration of bladder cancer cells by targeting HMGA1. BMC Urol 2019; 19:53. [PMID: 31196036 PMCID: PMC6567622 DOI: 10.1186/s12894-019-0485-1] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2018] [Accepted: 06/03/2019] [Indexed: 12/20/2022] Open
Abstract
Background Let-7 is one of the earliest discovered microRNAs(miRNAs) and has been reported to be down-regulated in multiple malignant tumors. The effects and molecular mechanisms of let-7i in bladder cancer are still unclear. This study was to investigate the effects and potential mechanisms of let-7i on bladder cancer cells. Methods Total RNA was extracted from bladder cancer cell lines. The expression levels of let-7i and HMGA1 were examined by quantitative real-time PCR. Cell viability was detected using the CCK-8 and colony formation assays, while transwell and wound healing assays were used to evaluate migration ability. Luciferase reporter assay and western blot were used to confirm the target gene of let-7i. Results Compared with the SV-40 immortalized human uroepithelial cell line (SV-HUC-1), bladder cancer cell lines T24 and 5637 had low levels of let-7i expression, but high levels of high mobility group protein A1 (HMGA1) expression. Transfection of cell lines T24 and 5637 with let-7i mimic suppressed cell proliferation and migration. Luciferase reporter assay confirmed HMGA1 may be one of the target genes of let-7i-5p. Protein and mRNA expression of HMGA1 was significantly downregulated in let-7i mimic transfected cell lines T24 and 5637. Conclusions Up-regulation of let-7i suppressed proliferation and migration of the human bladder cancer cell lines T24 and 5637 by targeting HMGA1. These findings suggest that let-7i might be considered as a novel therapeutic target for bladder cancer.
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Affiliation(s)
- M-M Qin
- Clinical Laboratory, The First Affiliated Hospital of Wannan Medical College, No.2, West Zheshan Road, Wuhu, 241001, Anhui, China
| | - X Chai
- Department of Urology, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241001, Anhui, China
| | - H-B Huang
- Department of Urology, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241001, Anhui, China
| | - G Feng
- Clinical Laboratory, The First Affiliated Hospital of Wannan Medical College, No.2, West Zheshan Road, Wuhu, 241001, Anhui, China
| | - X-N Li
- Clinical Laboratory, The First Affiliated Hospital of Wannan Medical College, No.2, West Zheshan Road, Wuhu, 241001, Anhui, China
| | - J Zhang
- Clinical Laboratory, The First Affiliated Hospital of Wannan Medical College, No.2, West Zheshan Road, Wuhu, 241001, Anhui, China
| | - R Zheng
- Clinical Laboratory, The First Affiliated Hospital of Wannan Medical College, No.2, West Zheshan Road, Wuhu, 241001, Anhui, China
| | - X-C Liu
- Clinical Laboratory, The First Affiliated Hospital of Wannan Medical College, No.2, West Zheshan Road, Wuhu, 241001, Anhui, China
| | - C Pu
- Clinical Laboratory, The First Affiliated Hospital of Wannan Medical College, No.2, West Zheshan Road, Wuhu, 241001, Anhui, China.
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Wu X, Shen J, Xiao Z, Li J, Zhao Y, Zhao Q, Cho CH, Li M. An overview of the multifaceted roles of miRNAs in gastric cancer: Spotlight on novel biomarkers and therapeutic targets. Biochem Pharmacol 2019; 163:425-439. [PMID: 30857828 DOI: 10.1016/j.bcp.2019.03.011] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2018] [Accepted: 03/07/2019] [Indexed: 02/07/2023]
Abstract
MicroRNAs (miRNAs) are a group of small non-coding RNAs that have displayed strong association with gastric cancer (GC). Through the repression of target mRNAs, miRNAs regulate many biological pathways that are involved in cell proliferation, apoptosis, migration, invasion, metastasis as well as drug resistance. The detection of miRNAs in tissues and in body fluids emerges as a promising method in the diagnosis and prognosis of GC, due to their unique expression pattern in correlation with GC. Notably, miRNAs are also identified as potential therapeutic targets for GC therapy. The present review is thus to highlight the multifaceted roles of miRNAs in GC and in GC therapies, which would give indications for future research.
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Affiliation(s)
- Xu Wu
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, China; South Sichuan Institute of Translational Medicine, Luzhou 646000, Sichuan, China
| | - Jing Shen
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, China; South Sichuan Institute of Translational Medicine, Luzhou 646000, Sichuan, China
| | - Zhangang Xiao
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, China; South Sichuan Institute of Translational Medicine, Luzhou 646000, Sichuan, China
| | - Jing Li
- Department of Oncology and Hematology, Hospital (T.C.M.) Affiliated to Southwest Medical University, Luzhou 646000, Sichuan, China
| | - Yueshui Zhao
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, China; South Sichuan Institute of Translational Medicine, Luzhou 646000, Sichuan, China
| | - Qijie Zhao
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, China; South Sichuan Institute of Translational Medicine, Luzhou 646000, Sichuan, China
| | - Chi Hin Cho
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, China; South Sichuan Institute of Translational Medicine, Luzhou 646000, Sichuan, China.
| | - Mingxing Li
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, China; South Sichuan Institute of Translational Medicine, Luzhou 646000, Sichuan, China.
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Lv J, Guo L, Wang JH, Yan YZ, Zhang J, Wang YY, Yu Y, Huang YF, Zhao HP. Biomarker identification and trans-regulatory network analyses in esophageal adenocarcinoma and Barrett's esophagus. World J Gastroenterol 2019; 25:233-244. [PMID: 30670912 PMCID: PMC6337015 DOI: 10.3748/wjg.v25.i2.233] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Revised: 12/10/2018] [Accepted: 12/15/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Esophageal adenocarcinoma (EAC) is an aggressive disease with high mortality and an overall 5-year survival rate of less than 20%. Barrett's esophagus (BE) is the only known precursor of EAC, and patients with BE have a persistent and excessive risk of EAC over time. Individuals with BE are up to 30-125 times more likely to develop EAC than the general population. Thus, early detection of EAC and BE could significantly improve the 5-year survival rate of EAC. Due to the limitations of endoscopic surveillance and the lack of clinical risk stratification strategies, molecular biomarkers should be considered and thoroughly investigated. AIM To explore the transcriptome changes in the progression from normal esophagus (NE) to BE and EAC. METHODS Two datasets from the Gene Expression Omnibus (GEO) in NCBI Database (https://www.ncbi.nlm.nih.gov/geo/) were retrieved and used as a training and a test dataset separately, since NE, BE, and EAC samples were included and the sample sizes were adequate. This study identified differentially expressed genes (DEGs) using the R/Bioconductor project and constructed trans-regulatory networks based on the Transcriptional Regulatory Element Database and Cytoscape software. Enrichment of Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) terms was identified using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) Bioinformatics Resources. The diagnostic potential of certain DEGs was assessed in both datasets. RESULTS In the GSE1420 dataset, the number of up-regulated DEGs was larger than that of down-regulated DEGs when comparing EAC vs NE and BE vs NE. Among these DEGs, five differentially expressed transcription factors (DETFs) displayed the same trend in expression across all the comparison groups. Of these five DETFs, E2F3, FOXA2, and HOXB7 were up-regulated, while PAX9 and TFAP2C were down-regulated. Additionally, the majority of the DEGs in trans-regulatory networks were up-regulated. The intersection of these potential DEGs displayed the same direction of changes in expression when comparing the DEGs in the GSE26886 dataset to the DEGs in trans-regulatory networks above. The receiver operating characteristic curve analysis was performed for both datasets and found that TIMP1 and COL1A1 could discriminate EAC from NE tissue, while REG1A, MMP1, and CA2 could distinguish BE from NE tissue. DAVID annotation indicated that COL1A1 and MMP1 could be potent biomarkers for EAC and BE, respectively, since they participate in the majority of the enriched KEGG and GO terms that are important for inflammation and cancer. CONCLUSION After the construction and analyses of the trans-regulatory networks in EAC and BE, the results indicate that COL1A1 and MMP1 could be potential biomarkers for EAC and BE, respectively.
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Affiliation(s)
- Jing Lv
- Department of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
| | - Lei Guo
- Department of Spinal Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
| | - Ji-Han Wang
- Department of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
| | - Yu-Zhu Yan
- Department of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
| | - Jun Zhang
- Department of Gastroenterology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
| | - Yang-Yang Wang
- The Tenth Research Institute of Telecommunications Technology, Xi’an 710000, Shaanxi Province, China
| | - Yan Yu
- Department of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
| | - Yun-Fei Huang
- Department of Spinal Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
| | - He-Ping Zhao
- Department of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
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