Bangming Pu1,
Yong Cao2,
Yan Li2,
Li Tang2,
Jiyi Xia3,
Bo Li1
1Department of Hepatobiliary Surgery;
2Medicine Experimental Center, The Affiliated Hospital of South West Medical University;
3School of Medical Information and Engineering, Southwest Medical University, Luzhou 646000, China.
For correspondence:- Bo Li
Email: liboer2012@163.com Tel:+868303160048
Accepted: 20 December 2019
Published: 31 January 2020
Citation:
Pu B, Cao Y, Li Y, Tang L, Xia J, Li B.
MiR-196b-5p regulates the proliferation of drug-resistant hepatocellular carcinoma cell lines by activating NF-κB/ABCB1 signaling pathway. Trop J Pharm Res 2020; 19(1):39-44
doi:
10.4314/tjpr.v19i1.6
© 2020 The authors.
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Abstract
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 NFκBIA 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 NFκBIA expression in HepG2 cells by binding to a response element in the 3′ UTR of NFκBIA. Further investigation showed that NFκBIA interacts with NFκB1 and reduces the concentration of NFκB1 in HepG2 cells. The promoter of ATP-binding cassette sub-family B member 1 (ABCB1) was also targeted and bound by NFκB1, 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 NFκB/ABCB1 signaling pathway.
Keywords: Hepatocellular carcinoma, miR-196b-5p, NF_4;BIA, NF_4;B1, ABCB1