Micro RNA-548a-5p promotes proliferation and inhibits apoptosis in hepatocellular carcinoma cells by targeting Tg737

AIM: To investigate whether Tg737 is regulated by micro RNA-548a-5p(mi R-548a-5p), and correlates with hepatocellular carcinoma(HCC) cell proliferation and apoptosis.METHODS: Assays of loss of function of Tg737 were performed by the colony formation assay, CCK assay and cell cycle assay in HCC cell lines. The interaction between mi R-548a-5p and its downstream target, Tg737, was evaluated by a dual-luciferase reporter assay and quantitative real-time polymerase chain reaction. Tg737 was then up-regulated in HCC cells to evaluate its effect on mi R-548a-5p regulation. Hep G2 cells stably overexpressing mi R-548a-5p or mi R-control were also subcutaneously inoculated into nude mice to evaluate the effect of mi R-548a-5p up-regulation on in vivo tumor growth. As the final step, the effect of mi R-548a-5p on the apoptosis induced by cisplatin was evaluated by flow cytometry.RESULTS: Down-regulation of Tg737, which is a target gene of mi R-548a-5p, accelerated HCC cell proliferation, and mi R-548a-5p promoted HCC cell proliferation in vitro and in vivo. Like the downregulation of Tg737, overexpression of mi R-548a-5p in HCC cell lines promoted cell proliferation, increased colony forming ability and hampered cell apoptosis. In addition, mi R-548a-5p overexpression increased HCC cell growth in vivo. Mi R-548a-5p downregulated Tg737 expression through direct contact with its 3' untranslated region(UTR), and mi R-548a-5p expression was negatively correlated with Tg737 levels in HCC specimens. Restoring Tg737(without the 3'UTR) significantly hampered mi R-548a-5p induced cell proliferation, and rescued the mi R-548a-5p induced cell proliferation inhibition and apoptosis induced by cisplatin.CONCLUSION: Mi R-548a-5p negatively regulates the tumor inhibitor gene Tg737 and promotes tumorigenesis in vitro and in vivo, indicating its potential as a novel therapeutic target for HCC.