1. MicroRNA-125b reverses oxaliplatin resistance in hepatocellular carcinoma by negatively regulating EVA1A mediated autophagy
- Author
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Ren, Wei-Wei, Li, Dan-Dan, Chen, Xiaolan, Li, Xiao-Long, He, Ya-Ping, Guo, Le-Hang, Liu, Lin-Na, Xu, Hui-Xiong, Sun, Li-Ping, and Zhang, Xiao-Ping
- Subjects
0301 basic medicine ,Cancer Research ,Immunology ,Article ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Downregulation and upregulation ,Lysosome ,microRNA ,medicine ,lcsh:QH573-671 ,neoplasms ,lcsh:Cytology ,Cell growth ,Chemistry ,Autophagy ,Signal transducing adaptor protein ,Cell Biology ,digestive system diseases ,Transmembrane protein ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Cancer research ,Ectopic expression - 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.
- Published
- 2018