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

• Published in: BMC cancer Vol. 14; no. 1; p. 97
• Main Authors: Zou, Chengcheng, Li, Yongguo, Cao, Yiyi, Zhang, Jinnan, Jiang, Jingrong, Sheng, Yanrui, Wang, Sen, Huang, Ailong, Tang, Hua
• Format: Journal Article
• Language: English
• Published: England BioMed Central 17.02.2014; BioMed Central Ltd
• Subjects: Animals; Carcinogenesis - metabolism; Carcinogenesis - pathology; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - virology; Cell cycle; Cell growth; Disease Progression; E2F5 Transcription Factor - biosynthesis; Female; Genes; Hep G2 Cells; Hepatitis B virus; Hepatitis B virus - metabolism; Humans; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Liver Neoplasms - virology; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNAs - biosynthesis; Studies; Up-Regulation - physiology
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/1471-2407-14-97

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.