title: Up-regulated MicroRNA-181a induces carcinogenesis in hepatitis B virus-related hepatocellular carcinoma by targeting E2F5.
abstract: 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.
authors: Chengcheng
authors: C
authors: Zou
authors: Yongguo
authors: Y
authors: Li
authors: Yiyi
authors: Y
authors: Cao
authors: Jinnan
authors: J
authors: Zhang
authors: Jingrong
authors: J
authors: Jiang
authors: Yanrui
authors: Y
authors: Sheng
authors: Sen
authors: S
authors: Wang
authors: Ailong
authors: A
authors: Huang
authors: Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China. tanghua86162003@aliyun.com.
authors: Hua
authors: H
authors: Tang
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism* / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D018450:Disease Progression; D050700:E2F5 Transcription Factor / Q000096:biosynthesis*; D005260:Female; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D050700:E2F5 Transcription Factor; C092558:E2F5 protein, human; C540193:MIrn181 microRNA, human; D035683:MicroRNAs