MicroRNA-125b reverses oxaliplatin resistance in hepatocellular carcinoma by negatively regulating EVA1A mediated autophagy

Cell Death & Disease
Wei-Wei RenXiao-Ping Zhang

Abstract

EVA1A (also known as transmembrane protein 166) is a transmembrane protein involved in the regulation of autophagy that acts as an adaptor protein to recruit or bind proteins in the lysosome or endoplasmic reticulum. In the present study, we identified EVA1A as a target of microRNA-125b (miR-125b), a member of a highly conserved family of miRNAs that has been proposed as a biomarker for hepatocellular carcinoma (HCC). Analysis of oxaliplatin-sensitive and oxaliplatin-resistant HCC cell lines showed that miR-125b is downregulated in resistant cells and its overexpression in sensitive cells decreased resistance to oxaliplatin by inhibiting cell proliferation, migration and epithelial-mesenchymal transition (EMT). EVA1A expression was shown to be upregulated in tissue samples from oxaliplatin-resistant HCC patients, and its ectopic expression partially induced autophagy and reversed the effect of miR-125b on inhibiting the growth of oxaliplatin-resistant cell lines and xenograft tumors. Taken together, our results suggest that miR-125b plays a role in the resistance of HCC cells to chemotherapy via a mechanism involving the downregulation of EVA1A-mediated autophagy.

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Citations

Jan 16, 2019·Cellular Oncology (Dordrecht)·Safieh Ebrahimi, Seyed Isaac Hashemy
Sep 9, 2020·Current Opinion in Pharmacology·Andrea LampisNicola Valeri
Jan 29, 2021·Cancer Communications·Guangtao PanShenglan Yang
Mar 14, 2021·Cell Death & Disease·Yafei WuQin Li
Mar 28, 2021·Acta Biochimica Et Biophysica Sinica·Hongmin CaoYejia Cui
Jul 3, 2021·International Journal of Molecular Sciences·Shizhen Zhao, Honggang Wang
May 1, 2021·Clinics and Research in Hepatology and Gastroenterology·Minghao YangXiao Cui
Aug 22, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Mohammad Hossein PourhanifehHamed Mirzaei

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Methods Mentioned

BETA
PCR
flow cytometry
confocal microscopy
transmission electron microscopy
xenograft
GTPase
transfection
Assay

Software Mentioned

Harmony Analysis
SPSS

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