Open Access Highly Accessed Research article

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

Chengcheng Zou12, Yongguo Li3, Yiyi Cao12, Jinnan Zhang12, Jingrong Jiang4, Yanrui Sheng12, Sen Wang12, Ailong Huang12 and Hua Tang12*

Author Affiliations

1 Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China

2 Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing 400016, China

3 Department of Forensic Medicine, Chongqing Medical University, Chongqing 400016, China

4 Infection Department of the First Affiliated Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu 610041, China

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BMC Cancer 2014, 14:97  doi:10.1186/1471-2407-14-97

Published: 17 February 2014



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.


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.


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.


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.

HCC; HBV; miR-181a; E2F5; Cell proliferation