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Yuan X, Zhou M, Liu X, Fan J, Chen L, Luo J, Li S, Zhou L. Identification of Biomarkers for Response to Interferon in Chronic Hepatitis B Based on Bioinformatics Analysis and Machine Learning. Viral Immunol 2025; 38:61-69. [PMID: 39992204 DOI: 10.1089/vim.2024.0091] [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] [Indexed: 02/25/2025] Open
Abstract
Interferon (IFN) is a pivotal agent against hepatitis B virus (HBV) in clinic, but there is a lack of accurate biomarkers to predict the response to IFN therapy in patients with chronic hepatitis B (CHB). Our study aimed to investigate potential targets for IFN therapy and to explore the network of interactions associated with IFN response. MicroRNA (miRNA) (GSE29911) and messenger RNA (GSE27555) datasets were used to screen the differentially expressed miRNAs (DEmiRNAs) and differentially expressed genes (DEGs). The random forest and k-nearest neighbors algorithm were used to further screen the core DEmiRNAs and build a prediction model. A Protein-Protein Interaction (PPI) network based on the STRING database was constructed and visualized by the Cytoscape software. Then, we collected transcription factors (TFs) from the TransmiR database to construct the TF-miRNA-hub gene regulatory network. Finally, real-time quantitative polymerase chain reaction was used to verify the expression of four miRNAs in HepG2-NTCP and Huh-7, and the effect of IFN treatment on four miRNAs' expression was preliminarily explored. Eighteen DEmiRNAs in GSE29911 and 700 DEGs in GSE27555 were identified. Boruta feature selection identified four miRNAs (miR-873, miR-200a, miR-30b, and let-7g) from 18 DEmiRNAs. We identified 48 TFs, 4 miRNAs, and 10 hub genes and constructed a TF-miRNA-hub gene network to suggest the mechanism of IFN response. According to the experimental results, miR-873 was upregulated and IFN treatment could inhibit it in HBV-transfected cells (p < 0.05). We constructed a TF-miRNA-hub gene regulatory network, and our results demonstrate that miR-873 was identified as a potential biomarker of IFN response in patients with CHB. This information provides an initial basis for understanding the complex IFN response regulatory mechanisms.
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Affiliation(s)
- Xiaoqin Yuan
- Department of Epidemiology, School of Public Health, Chongqing Medical University, Chongqing, China
| | - Mingsha Zhou
- Chongqing Hospital of The First Affiliated Hospital of Guangzhou University of Chinese Medicine (Chongqing Beibei Hospital of Traditional Chinese Medicine), Medical Records and Statistics Department, Chongqing, China
| | - Xing Liu
- Jiulongpo District Center for Disease Control and Prevention, Immunization Planning Department, Chongqing, China
| | - Jie Fan
- Chongqing Medical and Pharmaceutical College, School of Public Health and Emergency Management, Chongqing, China
| | - Lijuan Chen
- Department of Epidemiology, School of Public Health, Chongqing Medical University, Chongqing, China
| | - Jia Luo
- Department of Epidemiology, School of Public Health, Chongqing Medical University, Chongqing, China
| | - Shan Li
- Department of Epidemiology, School of Public Health, Chongqing Medical University, Chongqing, China
| | - Li Zhou
- Department of Epidemiology, School of Public Health, Chongqing Medical University, Chongqing, China
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Muchtar A, Onomura D, Ding D, Nishitsuji H, Shimotohno K, Okada S, Ueda K, Watashi K, Wakita T, Iida K, Yoshiyama H, Iizasa H. MicroRNA-3145 as a potential therapeutic target for hepatitis B virus: inhibition of viral replication via downregulation of HBS and HBX. Front Microbiol 2025; 15:1499216. [PMID: 39834379 PMCID: PMC11743939 DOI: 10.3389/fmicb.2024.1499216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Accepted: 12/02/2024] [Indexed: 01/22/2025] Open
Abstract
Current treatments for hepatitis B virus (HBV), such as interferons and nucleic acid analogs, have limitations due to side effects like depression and the development of drug-resistant mutants, highlighting the need for new therapeutic approaches. In this study, we identified microRNA-3145 (miR-3145) as a host-derived miRNA with antiviral activity that is upregulated in primary hepatocytes during HBV infection. The expression of its precursor, pri-miR-3145, increased in response to the the virus infection, and miR-3145 downregulated the hepatitis B virus S (HBS) antigen and hepatitis B virus X (HBX), thereby inhibiting viral replication. The binding site for miR-3145 was located in the HBV polymerase (pol) region, as experimentally confirmed. Moreover, overexpression of HBS and HBX induced pri-miR-3145 expression through endoplasmic reticulum stress. The expression of pri-miR-3145 showed a strong correlation with the Nance-Horan syndrome-like 1 (NHSL1) gene, as it is encoded within an intron of NHSL1, and higher NHSL1 expression in hepatocellular carcinoma patients with HBV infection was associated with better prognosis. These findings suggest that miR-3145-3p, along with small molecules targeting its binding sites, holds promise as a potential therapeutic candidate for HBV treatment.
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Affiliation(s)
- Amrizal Muchtar
- Department of Microbiology, Faculty of Medicine, Shimane University, Izumo, Japan
- Faculty of Medicine, Universitas Muslim Indonesia, Makassar, Indonesia
| | - Daichi Onomura
- Department of Microbiology, Faculty of Medicine, Shimane University, Izumo, Japan
- Division of Virology, Department of Infection and Immunity, Jichi Medical University, Shimotsuke, Japan
| | - Dan Ding
- Department of Microbiology, Faculty of Medicine, Shimane University, Izumo, Japan
- Department of Pathology, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Hironori Nishitsuji
- Department of Virology and Parasitology, Fujita Health University School of Medicine, Toyoake, Japan
| | - Kunitada Shimotohno
- Genome Medical Sciences Project, National Center for Global Health and Medicine, Ichikawa, Japan
| | - Shunpei Okada
- Department of Microbiology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Keiji Ueda
- Division of Virology, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Koichi Watashi
- Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
| | - Takaji Wakita
- Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
| | - Kei Iida
- Faculty of Science and Engineering, Kindai University, Higashiōsaka, Japan
- Center for Cancer Immunotherapy and Immunobiology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Hironori Yoshiyama
- Department of Microbiology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Hisashi Iizasa
- Department of Microbiology, Faculty of Medicine, Shimane University, Izumo, Japan
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Zhang B, Ma X, Zhou Y, Zhu B, Yu J, Liu H, Ma Y, Luan Y, Chen M. Diagnostic Value of Circulating microRNAs for Hepatocellular Carcinoma: Results of a Meta-analysis and Validation. Biochem Genet 2025:10.1007/s10528-024-11001-2. [PMID: 39751721 DOI: 10.1007/s10528-024-11001-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Accepted: 12/09/2024] [Indexed: 01/04/2025]
Abstract
Mounting evidence suggests that circulating microRNAs (miRNAs) hold diagnostic value in various malignancies. To identify circulating miRNAs for the early diagnosis of hepatocellular carcinoma (HCC), we conducted a meta-analysis to evaluate the diagnostic utility of miRNAs in HCC and further validated the results of the meta-analysis. English articles published prior to December 2023 were retrieved from databases including PubMed, Embase, and Web of Science. A random-effects or fixed-effects model was applied depending on the heterogeneity among studies. The pooled sensitivity, specificity, and the area under the summary receiver operating characteristic curve (AUC) were calculated to assess diagnostic accuracy. Additionally, RT-qPCR and receiver operating characteristic (ROC) analyses were employed to further validate the findings. A total of 36 studies were included, involving 3362 patients with HCC and 2150 patients with chronic hepatitis. The pooled sensitivity, specificity, and diagnostic odds ratio were 0.79 (95% CI 0.75-0.82), 0.79 (95% CI 0.73-0.84), and 14 (95% CI 9-22), respectively; the positive and negative likelihood ratios were 4.0 and 0.27, respectively; the area under the curve (AUC) in the summary receiver operating characteristic (ROC) was 0.85 (95% CI 0.82-0.88). Validation indicated a significant upregulation of miR-1246, miR-21, and miR-221 in HCC patients compared to those with chronic hepatitis (P < 0.01), while miR-122 and miR-26a were significantly downregulated (P < 0.01). Moreover, the validation results also demonstrated that serum levels of miR-21, miR-26a, miR-122, miR-221, and miR-1246 exhibit high sensitivity and specificity in the diagnosis of HCC. Circulating miRNAs may be promising biomarkers for HCC diagnosis.
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Affiliation(s)
- Bingqiang Zhang
- Qingdao Ruiside Medical Laboratory Co., LTD, Qingdao, 266111, Shandong, People's Republic of China
| | - Xiaoyan Ma
- Department of Oncology, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, 266111, Shandong, People's Republic of China
| | - Yang Zhou
- Qingdao Ruiside Medical Laboratory Co., LTD, Qingdao, 266111, Shandong, People's Republic of China
| | - Boyang Zhu
- School of Clinical and Basic Medical Sciences, Shandong First Medical, University& Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, People's Republic of China
| | - Junmei Yu
- Qingdao Ruiside Medical Laboratory Co., LTD, Qingdao, 266111, Shandong, People's Republic of China
| | - He Liu
- Qingdao Ruiside Medical Laboratory Co., LTD, Qingdao, 266111, Shandong, People's Republic of China
| | - Yongchao Ma
- College of Chemistry and Pharmaceutical Sciences, Qingdao Agricultural University, Qingdao, 266111, Shandong, People's Republic of China
| | - Yansong Luan
- Qingdao Ruiside Medical Laboratory Co., LTD, Qingdao, 266111, Shandong, People's Republic of China.
| | - Mengmeng Chen
- Qingdao Ruiside Medical Laboratory Co., LTD, Qingdao, 266111, Shandong, People's Republic of China.
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Yan R, Chen H, Selaru FM. Extracellular Vesicles in Hepatocellular Carcinoma: Progress and Challenges in the Translation from the Laboratory to Clinic. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1599. [PMID: 37763719 PMCID: PMC10534795 DOI: 10.3390/medicina59091599] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Revised: 08/27/2023] [Accepted: 08/31/2023] [Indexed: 09/29/2023]
Abstract
Extracellular vesicles (EVs) play critical roles in intercellular communication by transporting bioactive cargo to recipient cells. EVs have been implicated in a range of physiological and pathological processes, including tumor progression, metastasis, immune modulation, and drug resistance. The objective of this review is to present a thorough overview of recent studies focusing on EVs in hepatocellular carcinoma (HCC), with an emphasis on their potential utility as diagnostic biomarkers as well as therapeutic agents. Initially, we explore the utility of EVs as diagnostic biomarkers for HCC, followed by a discussion of their potential as carriers of therapeutic payloads. Additionally, we delve into the emerging field of therapeutic EVs for modulating tumor immune responses. Through this review, our ultimate aim is to provide a comprehensive understanding of the opportunities and challenges in the clinical translation of EV research in the domain of HCC.
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Affiliation(s)
- Rong Yan
- Department of Surgical Oncology, the First Affiliated Hospital, Xi’an Jiaotong University College of Medicine, Xi’an 710061, China
| | - Haiming Chen
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA;
| | - Florin M. Selaru
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA;
- Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD 21224, USA
- The Institute for Nanobiotechnology, The Johns Hopkins University, Baltimore, MD 21231, USA
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Zhang MH, Yuan YF, Liu LJ, Wei YX, Yin WY, Zheng LZY, Tang YY, Lv Z, Zhu F. Dysregulated microRNAs as a biomarker for diagnosis and prognosis of hepatitis B virus-associated hepatocellular carcinoma. World J Gastroenterol 2023; 29:4706-4735. [PMID: 37664153 PMCID: PMC10473924 DOI: 10.3748/wjg.v29.i31.4706] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 06/29/2023] [Accepted: 08/01/2023] [Indexed: 08/18/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a malignancy with a high incidence and fatality rate worldwide. Hepatitis B virus (HBV) infection is one of the most important risk factors for its occurrence and development. Early detection of HBV-associated HCC (HBV-HCC) can improve clinical decision-making and patient outcomes. Biomarkers are extremely helpful, not only for early diagnosis, but also for the development of therapeutics. MicroRNAs (miRNAs), a subset of non-coding RNAs approximately 22 nucleotides in length, have increasingly attracted scientists' attention due to their potential utility as biomarkers for cancer detection and therapy. HBV profoundly impacts the expression of miRNAs potentially involved in the development of hepatocarcinogenesis. In this review, we summarize the current progress on the role of miRNAs in the diagnosis and treatment of HBV-HCC. From a molecular standpoint, we discuss the mechanism by which HBV regulates miRNAs and investigate the exact effect of miRNAs on the promotion of HCC. In the near future, miRNA-based diagnostic, prognostic, and therapeutic applications will make their way into the clinical routine.
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Affiliation(s)
- Ming-He Zhang
- Department of Hepatobiliary & Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China
- State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei Province, China
| | - Yu-Feng Yuan
- Department of Hepatobiliary & Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China
| | - Li-Juan Liu
- State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei Province, China
| | - Yu-Xin Wei
- State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei Province, China
- Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - Wan-Yue Yin
- State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei Province, China
| | - Lan-Zhuo-Yin Zheng
- State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei Province, China
- Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China
| | - Ying-Ying Tang
- State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei Province, China
- Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China
| | - Zhao Lv
- State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei Province, China
| | - Fan Zhu
- State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei Province, China
- Hubei Province Key Laboratory of Allergy & Immunology, Wuhan University, Wuhan 430071, Hubei Province, China
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Ward JW, Wanlapakorn N, Poovorawan Y, Shouval D. Hepatitis B Vaccines. PLOTKIN'S VACCINES 2023:389-432.e21. [DOI: 10.1016/b978-0-323-79058-1.00027-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Identification of the Hub Genes and Potential Regulation Network in Chronic Hepatitis B via Bioinformatics Analysis. DISEASE MARKERS 2022; 2022:6113807. [PMID: 36193503 PMCID: PMC9525735 DOI: 10.1155/2022/6113807] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 08/19/2022] [Accepted: 08/29/2022] [Indexed: 12/02/2022]
Abstract
Background Chronic hepatitis B (CHB) is a serious infectious disease which is induced by hepatitis B virus (HBV) infection. This project was conducted to reveal the potential mechanism in CHB development via analyzing the public clinical data. Methods GSE33857 and GSE110217, obtained from the GEO database, were used for bioinformatics excavation. Briefly, the raw data of GSE33857 and GSE110217 were analyzed with the GEO2R, and then the expressed matrix files were generated. The matrix files was visualized as heat map with R software. The targets of the miRNAs were analyzed with the miRDIP database. The functional annotation and pathway enrichment were performed using “clusterProfiler” package in R software. The STRING database was utilized to analyze the interaction of the DEGs, and the PPI and miRNA-mRNA network were established according to the related results. Results 93 downregulated genes and 17 upregulated genes in GES33857, and 111 downregulated and 40 upregulated genes in GSE110217 were identified as the hub nodes. The targets of the DEGs in the datasets were enriched in PI3K/AKT and MAPK pathways and associated with transcriptional regulation. Moreover, PPI and miRNA-mRNA networks were also established with the DEGs and related targets in the datasets. miR-122-5p, miR-125b-5p, miR-136-5p, miR-194-5p, miR-139-5p, miR-140-5p, miR-181a-5p, and miR-29b-3p were identified as the potential biomarkers in CHB. Conclusion Eight miRNAs, including miR-122-5p, miR-125b-5p, miR-136-5p, miR-194-5p, miR-139-5p, miR-140-5p, miR-181a-5p, and miR-29b-3p, were identified as the potential biomarkers in CHB, and the PPI and miRNA-mRNA networks were also established.
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Letafati A, Najafi S, Mottahedi M, Karimzadeh M, Shahini A, Garousi S, Abbasi-Kolli M, Sadri Nahand J, Tamehri Zadeh SS, Hamblin MR, Rahimian N, Taghizadieh M, Mirzaei H. MicroRNA let-7 and viral infections: focus on mechanisms of action. Cell Mol Biol Lett 2022; 27:14. [PMID: 35164678 PMCID: PMC8853298 DOI: 10.1186/s11658-022-00317-9] [Citation(s) in RCA: 82] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Accepted: 01/26/2022] [Indexed: 02/06/2023] Open
Abstract
MicroRNAs (miRNAs) are fundamental post-transcriptional modulators of several critical cellular processes, a number of which are involved in host defense mechanisms. In particular, miRNA let-7 functions as an essential regulator of the function and differentiation of both innate and adaptive immune cells. Let-7 is involved in several human diseases, including cancer and viral infections. Several viral infections have found ways to dysregulate the expression of miRNAs. Extracellular vesicles (EV) are membrane-bound lipid structures released from many types of human cells that can transport proteins, lipids, mRNAs, and miRNAs, including let-7. After their release, EVs are taken up by the recipient cells and their contents released into the cytoplasm. Let-7-loaded EVs have been suggested to affect cellular pathways and biological targets in the recipient cells, and can modulate viral replication, the host antiviral response, and the action of cancer-related viruses. In the present review, we summarize the available knowledge concerning the expression of let-7 family members, functions, target genes, and mechanistic involvement in viral pathogenesis and host defense. This may provide insight into the development of new therapeutic strategies to manage viral infections.
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Affiliation(s)
- Arash Letafati
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Sajad Najafi
- Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mehran Mottahedi
- Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Karimzadeh
- Department of Virology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Ali Shahini
- Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Setareh Garousi
- Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Abbasi-Kolli
- Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Javid Sadri Nahand
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Michael R. Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, 2028 South Africa
| | - Neda Rahimian
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences (IUMS), Tehran, Iran
- Department of Internal Medicine, School of Medicine, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammad Taghizadieh
- Department of Pathology, School of Medicine, Center for Women’s Health Research Zahra, Tabriz University of Medical Sciences, Tabriz, Islamic Republic of Iran
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
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Zhang Q, Xu X, Wu M, Qin T, Wu S, Liu H. MiRNA Polymorphisms and Hepatocellular Carcinoma Susceptibility: A Systematic Review and Network Meta-Analysis. Front Oncol 2021; 10:562019. [PMID: 33542895 PMCID: PMC7851082 DOI: 10.3389/fonc.2020.562019] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Accepted: 12/03/2020] [Indexed: 12/11/2022] Open
Abstract
Background Hepatocellular carcinoma (HCC) is an intractable public health threat worldwide, representing the second leading cause of cancer-related mortality, with limited early detection and therapeutic options. Recent findings have revealed that the susceptibility of HCC is closely related to microRNA (miRNA). We performed this systematic review with a network meta-analysis to investigated four single nucleotide polymorphisms (SNPs) that most regularly reported in miRNAs, exploring their involvement in HCC susceptibility and interaction with hepatitis B virus (HBV). Methods Databases were reviewed for related studies published up to May 2019 to identify all studies that compared genotypes of miR-146a rs2910164, miR-149 rs2292832, miR-196a2 rs11614913, and miR-499 rs3746444 with no language and date restrictions. A pairwise meta-analysis was performed to estimate pooled odds ratios and 95% confidence intervals incorporating heterogeneity to assess the relationship between four miRNA polymorphisms and HCC. To further clarify the effect of polymorphisms on HCC, a Bayesian network meta-analysis was conducted to combine the effective sizes of direct and indirect comparisons. Calculations were performed by R version 3.6.1 and STATA 14.0. All steps were performed according to PRISMA guidelines. Results A total of 20 studies were enrolled in this network meta-analysis, providing 5,337 hepatocellular carcinoma cases and 6,585 controls. All included studies had an acceptable quality. Pairwise meta-analysis demonstrated that miR-196a2 rs11614913 was significantly associated with the susceptibility of HCC, while the other three SNPs were not found to have a significant association. In the analysis of HCC patients under different HBV infection status, only miR-196a2 revealed correlation of threefold risk. The network results showed no significant difference in the distribution of genotype frequencies except for miR-196a2, which appeared to have the highest superiority index when comparing and ranking four SNPs. Conclusion MiR-196a2 rs11614913 was significantly associated with the susceptibility of HCC, especially for HBV- related HCC, and that individuals with TC/CC were more susceptible. No significant association was found in the other three miRNA genes. MiR-196a2 could serve as the best predictor of susceptibility in HCC.
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Affiliation(s)
- Qimeng Zhang
- Department of Health Statistics, School of Public Health, China Medical University, Shenyang, China
| | - Xueying Xu
- Department of Health Statistics, School of Public Health, China Medical University, Shenyang, China
| | - Mingcheng Wu
- Department of Health Statistics, School of Public Health, China Medical University, Shenyang, China
| | - Tiantian Qin
- Department of Health Statistics, School of Public Health, China Medical University, Shenyang, China
| | - Shaoning Wu
- Department of Health Statistics, School of Public Health, China Medical University, Shenyang, China
| | - Hongbo Liu
- Department of Health Statistics, School of Public Health, China Medical University, Shenyang, China
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Liu AG, Pang YY, Chen G, Wu HY, He RQ, Dang YW, Huang ZG, Zhang R, Ma J, Yang LH. Downregulation of miR-199a-3p in Hepatocellular Carcinoma and Its Relevant Molecular Mechanism via GEO, TCGA Database and In Silico Analyses. Technol Cancer Res Treat 2020; 19:1533033820979670. [PMID: 33327879 PMCID: PMC7750904 DOI: 10.1177/1533033820979670] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
Existing reports have demonstrated that miR-199a-3p plays a role as a tumor suppressor in a variety of human cancers. This study aims to further validate the expression of miR-199a-3p in HCC and to explore its underlying mechanisms by using multiple data sets. Chip data or sequencing data and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were integrated to assess the expression of miR-199a-3p in HCC. The potential targets and transcription factor regulatory network of miR-199a-3p in HCC were determined and possible biological mechanism of miR-199a-3p was analyzed with bioinformatics methods. In the results, miR-199a-3p expression was significantly lower in HCC tissues compared to normal tissues according to chip data or sequencing data and qRT-PCR. Moreover, 455 targets of miR-199a-3p were confirmed, and these genes were involved in the PI3K-Akt signaling pathway, pathways in cancer, and focal adhesions. LAMA4 was considered a key target of miR-199a-3p. In CMTCN, 11 co-regulatory pairs, 3 TF-FFLs, and 2 composite-FFLs were constructed. In conclusion, miR-199a-3p was down regulated in HCC and LAMA4 may be a potential target of miR-199a-3p in HCC.
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Affiliation(s)
- An-Gui Liu
- Department of Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Yu-Yan Pang
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Gang Chen
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Hua-Yu Wu
- Departments of Cell Biology and Genetics, School of Pre-clinical Medicine, Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Rong-Quan He
- Department of Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Yi-Wu Dang
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Zhi-Guang Huang
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Rui Zhang
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Jie Ma
- Department of Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China.,Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Li-Hua Yang
- Department of Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China
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Cui G, Wang H, Liu W, Xing J, Song W, Zeng Z, Liu L, Wang H, Wang X, Luo H, Leng X, Shen S. Glycogen Phosphorylase B Is Regulated by miR101-3p and Promotes Hepatocellular Carcinoma Tumorigenesis. Front Cell Dev Biol 2020; 8:566494. [PMID: 33324633 PMCID: PMC7723997 DOI: 10.3389/fcell.2020.566494] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Accepted: 08/26/2020] [Indexed: 01/06/2023] Open
Abstract
Glycogen metabolism plays a key role in tumorigenesis. High expression levels of glycogen phosphorylase B (PYGB) were reported in several cancers and might be served as a prognostic biomarker for cancer from precancerous lesions. Previous studies indicated the high expression of PYGB in hepatocellular carcinoma (HCC) tissues. However, the detailed roles of PYGB in HCC, as well as the regulatory mechanisms, are still unclear. In this study, we confirmed that PYGB was overexpressed in HCC tissues. PYGB overexpression was significantly associated with an aggressive tumor phenotype and poor prognosis of HCC patients. Functionally, PYGB knockdown suppressed HCC cell proliferation, migration and invasion in vitro, as well as tumorigenesis and metastasis in vivo. Bioinformatics analysis indicated that PYGB overexpression might enhance epithelial to mesenchymal transition (EMT) in HCC. Moreover, miR-101-3p was identified to post-transcriptionally inhibit the expression of PYGB via binding to 3′-UTR of PYGB. Overexpression of PYGB antagonized the regulatory effect of miR-101-3p on cell proliferation, migration and invasion in HCC cells. In summary, our results suggest that miR-101-3p/PYGB axis has an important role in HCC and PYGB could be served as a novel prognostic biomarker and therapeutic target for improving the prognosis of HCC patients.
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Affiliation(s)
- Guangying Cui
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Huifen Wang
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Wenli Liu
- Clinical Laboratory Diagnostics, College of Medical Technology, Beihua University, Jilin, China
| | - Jiyuan Xing
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Wengang Song
- Clinical Laboratory Diagnostics, College of Medical Technology, Beihua University, Jilin, China
| | - Zhaohai Zeng
- Department of Infectious Diseases, Guangshan County People's Hospital, Xinyang, China
| | - Liwen Liu
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Haiyu Wang
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xuemei Wang
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Hong Luo
- Department of Infectious Diseases, Guangshan County People's Hospital, Xinyang, China
| | - Xiaoyang Leng
- Department of Infectious Diseases, Guangshan County People's Hospital, Xinyang, China
| | - Shen Shen
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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12
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Zhang C, Liu P, Zhang C. Hepatitis B virus X protein upregulates alpha-fetoprotein to promote hepatocellular carcinoma by targeting miR-1236 and miR-329. J Cell Biochem 2020; 121:2489-2499. [PMID: 31680299 DOI: 10.1002/jcb.29471] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Accepted: 10/10/2019] [Indexed: 12/29/2022]
Abstract
Hepatitis B virus (HBV) infection is the most common cause of hepatocellular carcinoma (HCC) worldwide, wherein the expression of alpha-fetoprotein (AFP) is reactivated to promote tumorgenesis. Hepatitis B virus X protein (HBx) protein encoded by the HBV virus X gene has been considered to be oncogenic and implicated in hepatocarcinogenesis. However, the relationship between HBx and abnormal AFP expression in HCC is yet to be fully understood. To explore the potential regulation of HBx on AFP re-expression in HCC, 97 HCC samples of different etiologies were analyzed, and extremely higher serum AFP levels were found in patients with HBsAg+ . Analyses of HBV-related HCC specimens showed that the expression of AFP was negatively correlated with the levels of miR-1236 and miR-329. Further analyses indicated that HBx promotes the expression of AFP by orchestrating the levels of miR-1236 and miR-329 both in vitro and in vivo. Specifically, miR-1236 and miR-329 bind to the potential target sequences in AFP mRNA 3'-untranslated region to suppress its expression. HBx transfection resulted in the significant decrement of these microRNAs and increment of AFP expression. Moreover, AFP promotes the proliferation of hepatoma cells and attenuates the proapoptotic effect of chemotherapy agents. These findings revealed a novel regulatory mechanism of HBx on the abnormal AFP expression in HCC, which may provide a therapeutic approach for combating HBV-related HCC by targeting the regulation of AFP expression.
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Affiliation(s)
- Chao Zhang
- National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology, Beijing Engineering Research Center of Laboratory Medicine, Beijing, China
| | - Peng Liu
- Department of Scientific Research, Central Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Chuanbao Zhang
- National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology, Beijing Engineering Research Center of Laboratory Medicine, Beijing, China
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13
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Ge Y, Mu W, Ba Q, Li J, Jiang Y, Xia Q, Wang H. Hepatocellular carcinoma-derived exosomes in organotropic metastasis, recurrence and early diagnosis application. Cancer Lett 2020; 477:41-48. [PMID: 32112905 DOI: 10.1016/j.canlet.2020.02.003] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Revised: 11/21/2019] [Accepted: 02/06/2020] [Indexed: 12/17/2022]
Abstract
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, despite improvements in the clinical trial and diagnosis, HCC still remains high mortality due to the 70% recurrence and lung metastasis after surgical resection. Exosomes are small membrane vesicles, which are shuttled from donor cells to recipient cells, contributing to the recruitment and reprogramming of constituents via an autocrine or paracrine fashion. HCC derived exosomes could redirect metastasis of tumor cells which lack the capacity to metastasize to a specific organ via generating pre-metastatic niche. These findings emphasize a practical and potentially feasible role of exosomes in the treatment of patients with HCC, both as a target and a vehicle for drug design. We herein summarize recent findings that implicate oncogenes and non-canonical signaling of HCC exosomes, as well as the impact of exosomal bioactive molecules in high recurrence induced by organ-specific metastasis. The aim of review is to illustrate the underlying mechanism of exosomes in tumor metastasis, immune evasion, and the potential application of prognostic biomarker in HCC process.
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Affiliation(s)
- Yang Ge
- State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, 200032, China
| | - Wei Mu
- State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, 200032, China
| | - Qian Ba
- State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, 200032, China
| | - Jingquan Li
- State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, 200032, China
| | - Yiguo Jiang
- School of Public Health, Guangzhou Medical University, Guangzhou, 511436, China
| | - Qiang Xia
- Organ Transplantation Center, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China.
| | - Hui Wang
- State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, 200032, China.
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14
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Ni X, Lin Z, Dai S, Chen H, Chen J, Zheng C, Wu B, Ao J, Shi K, Sun H. Screening and verification of microRNA promoter methylation sites in hepatocellular carcinoma. J Cell Biochem 2020; 121:3626-3641. [PMID: 32065423 DOI: 10.1002/jcb.29656] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Accepted: 12/19/2019] [Indexed: 12/18/2022]
Abstract
The promoter methylation mode of microribonucleic acid (miRNA) plays a crucial role in the process of hepatocellular carcinoma (HCC). Therefore, the primary purpose of this study was to screen and verify the miRNA methylation sites associated with the overall survival (OS) and clinical characteristics of HCC patients. Methylation-related data were from the Cancer Genome Atlas (TCGA). R software was utilized to screen the methylation sites. The least absolute shrinkage and selection operator algorithm was utilized to develop the miRNA promoter methylation models. Then, methylation-specific polymerase chain reaction was performed with 146 HCC tissues to verify the accuracy of the vascular infiltration-related model. Additionally, we verified the functions of vascular infiltration-related miRNA by utilizing cells transfected with miR-199a-3p mimic. The model for predicting OS of HCC patients contained eight methylation sites. The Kaplan-Meier analysis suggested that the model could divide HCC patients into high- and low-risk groups (P < .0001). COX regression analysis suggested that the model (P < .001; 95% CI, 1.264-2.709) and T category (P < .001; 95% CI, 1.472-3.119) were independent risk factors for affecting OS of HCC patients. The model for predicting vascular infiltration, pathological grade, and clinical stage contained 7, 10, and 9 methylation sites respectively, with their area under the receiver operating characteristic curve (AUC) values 0.667, 0.745, and 0.725, respectively. The functional analysis suggested that miRNA methylation is involved in various biological processes such as WNT, MAPK, and mTOR signaling pathways. The accuracy of the vascular infiltration-related model was consistent with our previous bioinformatics assay. And upregulation of miR-199a-3p decreased migration and invasion abilities. The screened miRNA promoter methylation sites can be served as biomarkers for judging OS, vascular infiltration, pathology grade, and clinical stage. It can also provide new targets for improving the treatment and prognosis of HCC patients.
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Affiliation(s)
- Xiaofeng Ni
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Zhuo Lin
- Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.,Wenzhou Key Laboratory of Hepatology, Wenzhou, Zhejiang, China.,Hepatology Institute of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Shengjie Dai
- Department of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Hao Chen
- Department of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Jianhui Chen
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.,Chinese Academy of Sciences Shanghai Branch, Shanghai, China
| | - Chenlei Zheng
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Boda Wu
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Jianyang Ao
- Department of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Keqing Shi
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.,Laboratory of Precision Medicine Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Hongwei Sun
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.,Department of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
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15
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Wu SM, Li TH, Yun H, Ai HW, Zhang KH. miR-140-3p Knockdown Suppresses Cell Proliferation and Fibrogenesis in Hepatic Stellate Cells via PTEN-Mediated AKT/mTOR Signaling. Yonsei Med J 2019; 60:561-569. [PMID: 31124340 PMCID: PMC6536388 DOI: 10.3349/ymj.2019.60.6.561] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Revised: 01/07/2019] [Accepted: 02/14/2019] [Indexed: 12/14/2022] Open
Abstract
PURPOSE Liver fibrosis is a major cause of morbidity and mortality and the outcome of various chronic liver diseases. Activation of hepatic stellate cells (HSCs) is the key event in liver fibrosis. Studies have confirmed that miR-140-3p plays a potential regulatory effect on HSC activation. However, whether miR-140-3p mediates the liver fibrosis remains unknown. MATERIALS AND METHODS Expression of miR-140-3p was detected by real-time quantitative PCR (qPCR). Cell proliferation was measured by MTT, while cell apoptosis rate was determined via flow cytometry. Western blot assay was used to detect the expression of cleaved PARP. The fibrogenic effect was evaluated by expression of α-smooth muscle actin and desmin. Functional experiments were performed in transforming growth factor β1 (TGF-β1)-induced HSC-T6 cells with transfection of anti-miR-140-3p and/or siPTEN. Target binding between miR-140-3p and PTEN was predicted by the TargetScan database and identified using luciferase reporter assay and RNA immunoprecipitation. RESULTS TGF-β1 induced the activation of HSC-T6 cells, and miR-140-3p expression varied according to HSC-T6 cell activation status. Knockdown of miR-140-3p reduced cell proliferation and the expressions of α-SMA and desmin, as well as increased apoptosis, in TGF-β1-induced HSC-T6 cells, which could be blocked by PTEN silencing. Additionally, inactivation of the AKT/mTOR signaling pathway stimulated by miR-140-3p knockdown was abolished when silencing PTEN expression. PTEN was negatively regulated by miR-140-3p via direct binding in HSC-T6 cells. CONCLUSION miR-140-3p is an important mediator in HSC-T6 cell activation, and miR-140-3p knockdown suppresses cell proliferation and fibrogenesis in TGF-β1-induced HSC-T6 cells, indicating that miR-140-3p may be a potential novel molecular target for liver fibrosis.
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Affiliation(s)
- Shi Min Wu
- Wuhan Center for Clinical Laboratory, Wuhan Forth Hospital; Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tian Hong Li
- Department of Ophthalmology, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hao Yun
- Wuhan Center for Clinical Laboratory, Wuhan Forth Hospital; Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hong Wu Ai
- Department of Clinical Laboratory, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ke Hui Zhang
- Wuhan Center for Clinical Laboratory, Wuhan Forth Hospital; Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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16
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Chang CM, Wong HSC, Huang CY, Hsu WL, Maio ZF, Chiu SJ, Tsai YT, Chen BK, Wan YJY, Wang JY, Chang WC. Functional Effects of let-7g Expression in Colon Cancer Metastasis. Cancers (Basel) 2019; 11:489. [PMID: 30959863 PMCID: PMC6521310 DOI: 10.3390/cancers11040489] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Revised: 03/25/2019] [Accepted: 03/28/2019] [Indexed: 12/20/2022] Open
Abstract
MicroRNA regulation is crucial for gene expression and cell functions. It has been linked to tumorigenesis, development and metastasis in colorectal cancer (CRC). Recently, the let-7 family has been identified as a tumor suppressor in different types of cancers. However, the function of the let-7 family in CRC metastasis has not been fully investigated. Here, we focused on analyzing the role of let-7g in CRC. The Cancer Genome Atlas (TCGA) genomic datasets of CRC and detailed data from a Taiwanese CRC cohort were applied to study the expression pattern of let-7g. In addition, in vitro as well as in vivo studies have been performed to uncover the effects of let-7g on CRC. We found that the expression of let-7g was significantly lower in CRC specimens. Our results further supported the inhibitory effects of let-7g on CRC cell migration, invasion and extracellular calcium influx through store-operated calcium channels. We report a critical role for let-7g in the pathogenesis of CRC and suggest let-7g as a potential therapeutic target for CRC treatment.
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Affiliation(s)
- Che-Mai Chang
- Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei 110, Taiwan.
- Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei 110, Taiwan.
- Ph.D. for Medical Biotechnology Program, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan.
| | - Henry Sung-Ching Wong
- Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei 110, Taiwan.
- Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei 110, Taiwan.
| | - Chien-Yu Huang
- Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
- Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei 235, Taiwan.
| | - Wen-Li Hsu
- Research Organization for Nano & Life Innovation, Waseda University, Tokyo 162-8480, Japan.
- Emerging Compounds Research Center, Department of Environmental Science and Engineering, College of Engineering, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan.
- Department of Medical Research, E-DA Hospital, I-Shou University, Kaohsiung 84001, Taiwan.
| | - Zhi-Feng Maio
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
| | - Siou-Jin Chiu
- Department of Medical Genetics, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
| | - Yao-Ting Tsai
- Department of Medical Genetics, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
| | - Ben-Kuen Chen
- Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
| | - Yu-Jui Yvonne Wan
- Department of Medical Pathology and Laboratory Medicine, University of California, Davis, Sacramento, CA 95817, USA.
| | - Jaw-Yuan Wang
- Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei 110, Taiwan.
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
- Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
| | - Wei-Chiao Chang
- Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei 110, Taiwan.
- Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei 110, Taiwan.
- Department of Pharmacy, Taipei Medical University-Wanfang Hospital, Taipei 116, Taiwan.
- Department of Medicine Research, Taipei Medical University-Shuang Ho Hospital, New Taipei City 235, Taiwan.
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17
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Tang B, Bao N, He G, Wang J. Long noncoding RNA HOTAIR regulates autophagy via the miR-20b-5p/ATG7 axis in hepatic ischemia/reperfusion injury. Gene 2019; 686:56-62. [DOI: 10.1016/j.gene.2018.10.059] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2018] [Revised: 10/19/2018] [Accepted: 10/20/2018] [Indexed: 02/08/2023]
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18
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Lu HM, Yi WW, Ma YS, Wu W, Yu F, Fan HW, Lv ZW, Yang HQ, Chang ZY, Zhang C, Xie WT, Jiang JJ, Song YC, Chai L, Jia CY, Lu GX, Zhong XJ, Hou LK, Wu CY, Shi MX, Liu JB, Fu D. Prognostic implications of decreased microRNA-101-3p expression in patients with non-small cell lung cancer. Oncol Lett 2018; 16:7048-7056. [PMID: 30546438 PMCID: PMC6256371 DOI: 10.3892/ol.2018.9559] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2018] [Accepted: 08/21/2018] [Indexed: 12/11/2022] Open
Abstract
To investigate the expression level of microRNA-101-3p (miR-101-3p) and its possible association with progression, prognosis and chemotherapy in patients with non-small cell lung cancer (NSCLC), the Gene Expression Omnibus (GEO) database was used. Quantitative polymerase chain reaction was used to verify the expression in 327 NSCLC and 42 adjacent normal lung tissues, of which 42 viable tissues were paired with nearby normal lung tissues. Based on the Cox regression model, univariate and multivariate analyses were used to address the factors that had effects on overall survival (OS) and disease-free survival (DFS) rate. Data from the GEO database demonstrated that the miR-101-3p expression in NSCLC was downregulated, compared with normal lung cancer. Survival analysis through univariate and multivariate models indicated that the miR-101-3p expression level was a crucial risk factor for OS and DFS in patients with NSCLC. A number of clinical parameters were determined to be associated with miR-101-3p expression, including tumor diameter, lymph node metastasis and tumor-node-metastasis stage. Adjuvant chemotherapy with high expression of miR-101-3p was determined to increase OS and DFS in patients with NSCLC, compared with patients with de novo or low expression of miR-101-3p. The present results demonstrated that miR-101-3p expression levels were associated with NSCLC progression and prognosis, which indicated that miR-101-3p may serve as a biomarker for patients with NSCLC who have received adjuvant chemotherapy.
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Affiliation(s)
- Hai-Min Lu
- Department of Thoracic Surgery, Nantong Tumor Hospital, Nantong, Jiangsu 226631, P.R. China
| | - Wan-Wan Yi
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
| | - Yu-Shui Ma
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.,Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, College of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, P.R. China
| | - Wei Wu
- Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, P.R. China
| | - Fei Yu
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
| | - Heng-Wei Fan
- Department of Hepatic Surgery I, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, P.R. China
| | - Zhong-Wei Lv
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
| | - Hui-Qiong Yang
- Department of Pathology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
| | - Zheng-Yan Chang
- Department of Pathology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
| | - Chao Zhang
- Department of Hepatic Surgery I, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, P.R. China
| | - Wen-Ting Xie
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
| | - Jun-Jian Jiang
- Department of Hand Surgery, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China
| | - Ying-Chun Song
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
| | - Li Chai
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
| | - Cheng-You Jia
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
| | - Gai-Xia Lu
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
| | - Xiao-Jun Zhong
- Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangsu 330006, P.R. China
| | - Li-Kun Hou
- Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, P.R. China
| | - Chun-Yan Wu
- Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, P.R. China
| | - Min-Xin Shi
- Department of Thoracic Surgery, Nantong Tumor Hospital, Nantong, Jiangsu 226631, P.R. China
| | - Ji-Bin Liu
- Department of Thoracic Surgery, Nantong Tumor Hospital, Nantong, Jiangsu 226631, P.R. China
| | - Da Fu
- Central Laboratory for Medical Research, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
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