Up-regulated MicroRNA-181a induces carcinogenesis in Hepatitis B virus-related hepatocellular carcinoma by targeting E2F5

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• 作者：Chengcheng Zou (18) (19)
  Yongguo Li (20)
  Yiyi Cao (18) (19)
  Jinnan Zhang (18) (19)
  Jingrong Jiang (21)
  Yanrui Sheng (18) (19)
  Sen Wang (18) (19)
  Ailong Huang (18) (19)
  Hua Tang (18) (19)
  
• 关键词：HCC ; HBV ; miR ; 181a ; E2F5 ; Cell proliferation
• 刊名：BMC Cancer
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：14
• 期：1
• 全文大小：1,042 KB
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  23. The pre-publication history for this paper can be accessed here: http://www.biomedcentral.com/1471-2407/14/97/prepub
  
• 作者单位：Chengcheng Zou (18) (19)
  Yongguo Li (20)
  Yiyi Cao (18) (19)
  Jinnan Zhang (18) (19)
  Jingrong Jiang (21)
  Yanrui Sheng (18) (19)
  Sen Wang (18) (19)
  Ailong Huang (18) (19)
  Hua Tang (18) (19)
  
  18. Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, China
  19. Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, 400016, China
  20. Department of Forensic Medicine, Chongqing Medical University, Chongqing, 400016, China
  21. Infection Department of the First Affiliated Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu, 610041, China
  
• ISSN：1471-2407

文摘

Background Accumulating evidence showed that microRNAs are involved in development and progression of multiple tumors. Recent studies have found that miR-181a were dysregulated in several types of cancers, however, the function of miR-181a in hepatocellular carcinoma (HCC) remains unclear. In this study we assessed the potential association between miR-181a, HBV and HCC. Methods The expression of miR-181a in HBV-expressing cells was determined by using qRT-PCR. Dual-Luciferase reporter Assay, qRT-PCR and western blot were performed to investigate the target genes of miR-181a. The effects of miR-181a on HCC proliferation were analyzed by MTS and colony formation assay. Tumor growth assay was used to analyze the effect of miR-181a on tumor formation. Results HBV up-regulated miR-181a expression by enhancing its promoter activity. Overexpression of miR-181a in hepatoma cells promoted cell growth in vitro and tumor formation in vivo. Conversely, inhibition of miR-181a suppressed the proliferation of HBV-expressing cells. Mechanism investigation revealed that miR-181a inhibited the expression of transcription factor E2F5 by specifically targeting its mRNA 3′UTR. Moreover, E2F5 inhibition induced cell growth and rescued the suppressive effect of miR-181a inhibitor on the proliferation of SMMC-7721 cells. Interestingly, we also discovered that HBV could down-regulate E2F5 expression. Conclusions Those results strongly suggested that HBV down-regulated E2F5 expression, in part, by up-regulating the expression of miR-181a. Up-regulation of miR-181a by HBV in hepatoma cells may contribute to the progression of HCC possibly by targeting E2F5, suggesting miR-181a plays important role in HCC development.