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.

Details

Title
MicroRNA-125b reverses oxaliplatin resistance in hepatocellular carcinoma by negatively regulating EVA1A mediated autophagy
Author
Wei-Wei, Ren 1 ; Dan-Dan, Li 1 ; Chen, Xiaolan 2 ; Xiao-Long, Li 1 ; He, Ya-Ping 1 ; Le-Hang, Guo 1 ; Lin-Na, Liu 1 ; Li-Ping, Sun 1 ; Zhang, Xiao-Ping 3 

 Tongji University School of Medicine, Department of Medical Ultrasound, Shanghai Tenth People’s Hospital, Ultrasound Research and Educational Institute, Shanghai, China (GRID:grid.24516.34) (ISNI:0000000123704535) 
 Tongji University School of Medicine, Department of Radiotherapy, Shanghai Tenth People’s Hospital, Ultrasound Research and Educational Institute, Shanghai, China (GRID:grid.24516.34) (ISNI:0000000123704535) 
 Tongji University School of Medicine, Department of Interventional & Vascular Surgery, Shanghai, China (GRID:grid.24516.34) (ISNI:0000000123704535) 
Publication year
2018
Publication date
May 2018
Publisher
Springer Nature B.V.
e-ISSN
20414889
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2621100995
Copyright
© The Author(s) 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.