Department of Infectious Diseases, The First People's Hospital of Kunshan, Kunshan, Jiangsu Province, P.R. China.
Oncol Res. 2019 Mar 29;27(4):449-458. doi: 10.3727/096504017X15016337254623. Epub 2017 Aug 11.
MicroRNAs, a class of endogenous noncoding RNAs, regulate gene expression at the posttranscriptional level and thus take part in multiple biological processes. An increasing number of miRNAs have been found to be dysregulated in hepatocellular carcinoma (HCC) and are involved in liver tumorigenesis. In this study, miR-125a-5p was found to be obviously downregulated much more in hepatitis B virus (HBV)-related HCC. To investigate the effects of miR-125a-5p, miR-125a-5p was overexpressed in HepG2.2.15 and HepG3X cells. The findings have indicated that overexpression of miR-125a-5p dramatically inhibited cell proliferation and induced cell apoptosis. Furthermore, overexpression of miR-125a-5p could significantly decrease the secretion of HBsAg and HBeAg. In concordance to this, the expression of ErbB3 was upregulated in human HBV-related HCC tissue, HepG2.2.15 cells, and HepG3X cells. miR-125a-5p directly targeted ErbB3 and reduced both mRNA and protein levels of ErbB3, which promoted cell proliferation and suppressed cell apoptosis in HCC cells. Our results provide new insights into the function of miR-125a-5p in HBV-related HCC. It is beneficial to gain insight into the mechanism of HBV infection and pathophysiology of HBV-related HCC.
MicroRNAs 是一类内源性非编码 RNA,在转录后水平调节基因表达,从而参与多种生物学过程。越来越多的研究发现 miRNA 在肝细胞癌(HCC)中失调,并参与肝癌的发生。本研究发现 miR-125a-5p 在乙型肝炎病毒(HBV)相关 HCC 中明显下调。为了研究 miR-125a-5p 的作用,我们在 HepG2.2.15 和 HepG3X 细胞中转染 miR-125a-5p。研究结果表明,miR-125a-5p 的过表达显著抑制细胞增殖并诱导细胞凋亡。此外,miR-125a-5p 的过表达可显著降低 HBsAg 和 HBeAg 的分泌。与此一致的是,ErbB3 在人 HBV 相关 HCC 组织、HepG2.2.15 细胞和 HepG3X 细胞中表达上调。miR-125a-5p 直接靶向 ErbB3,降低 ErbB3 的 mRNA 和蛋白水平,促进 HCC 细胞的增殖并抑制细胞凋亡。我们的研究结果为 miR-125a-5p 在 HBV 相关 HCC 中的功能提供了新的见解。这有助于深入了解 HBV 感染的机制和 HBV 相关 HCC 的病理生理学。