miR-34a and miR-125a-5p inhibit proliferation and metastasis but induce apoptosis in hepatocellular carcinoma cells via repressing the MACC1-mediated PI3K/AKT/mTOR pathway

Yan-Ming Zhang, Qun-Mei Wu, Li-Ying Chang,  Jun-Cai Liu

Abstract:

microRNA-34a (miR-34a) and microRNA-1251-5p (miR-125a-5p) were considered as tumor suppressors in hepatocellular carcinoma (HCC). Nevertheless, the modulatory mechanisms of miR-34a and miR-125a-5p in HCC haven’t been completely understood. The levels of metastasis-associated with colon cancer 1 (MACC1) and miRNAs (miR-34a and miR-125a-5p) were determined by quantitative real-time polymerase chain reaction (qRT-PCR), and the levels of associated proteins were detected by western blot assay. Cell proliferation and metastasis were examined via Cell Counting Kit-8 (CCK-8) and transwell assays, respectively. Cell apoptosis was measured through flow cytometry. The effect of MACC1 on HCC in vivo was explored via xenograft assay. Dual-luciferase reporter assay and RNA Immunoprecipitation (RIP) assay were implemented to explore the target correlation. The expression of MACC1 was upregulated in HCC tissues and cells. Knockdown of MACC1 inhibited proliferation and metastasis but expedited apoptosis of HCC cells and the repression of tumor growth in vivo was evoked by MACC1 downregulation. Both miR-34a and miR-125a-5p directly targeted MACC1 and repressed the expression of MACC1 in HCC cells. Overexpression of miR-34a or miR-125a-5p restrained cell proliferation and metastasis while induced apoptosis by downregulating MACC1 in HCC cells. miR-34a and miR-125a-5p repressed phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signal pathway via reducing MACC1 in HCC cells. miR-34a and miR-125a-5p refrained proliferation and metastasis while motivated apoptosis in HCC cells through the PI3K/AKT/mTOR pathway by repressing MACC1. miR-34a and miR-125a-5p might be splendid biomarkers in the therapeutic strategies for HCC.