MiR-196b-5p regulates the proliferation of drug-resistant hepatocellular carcinoma cell lines by activating NFkB/ABCB1 signaling pathway.

Purpose: To explore the molecular function of miR-196b-5p in hepatocellular carcinoma (HCC). Methods: MiR-196b-5p expression levels in HCC tissue samples were assessed by qRT-PCR. MiR- 196b-5p was knocked-down or over-expressed in HepG2 cells by transfecting the cells with plasmids expressing either a miR-196b-5p inhibitor or mimic, respectively, while cell proliferation was assessed by MTT assay. The interaction of miR-196b-5p with target molecules was confirmed using luciferase reporter assay. Cell cycle was investigated by flow cytometry, while NFkBIA expression was assessed by western blotting. Results: MiR-196b-5p was over-expressed in HCC, and miR-196b-5p expression levels in patients with HCC were related to tumor grade. MiR-196b-5p over-expression promoted cell proliferation and colony formation and suppressed cell cycle arrest and apoptosis. The results of luciferase reporter assay showed that miR-196b-5p reduced NFkBIA expression in HepG2 cells by binding to a response element in the 3' UTR of NFkBIA. Further investigation showed that NFkBIA interacts with NFkB1 and reduces the concentration of NFkB1 in HepG2 cells. The promoter of ATP-binding cassette sub-family B member 1 (ABCB1) was also targeted and bound by NFkB1, which altered the expression of ABCB1 in HepG2 cells. Conclusion: MiR-196b-5p regulates cell proliferation in drug-resistant HCC cell lines via activation of the NFkB/ABCB1 signaling pathway. [ABSTRACT FROM AUTHOR]