MiR-34a Mediates Oxaliplatin Resistance of Colorectal Cancer Cells by Inhibiting Macroautophagy Transforming Growth Factor-β/Smad4 Pathway

Overview

Journal World J Gastroenterol

Publisher Baishideng Publishing Group

Specialty Gastroenterology

Date 2017 Mar 29

PMID 28348487

Citations 53

Authors

Chen Sun

Fu-Jing Wang

Hao-Gang Zhang

Xun-Zheng Xu

Rui-Chun Jia

Lei Yao

Peng-Fei Qiao

Affiliations

Soon will be listed here.

Abstract

Aim: To investigate whether microRNA (miR)-34a mediates oxaliplatin (OXA) resistance of colorectal cancer (CRC) cells by inhibiting macroautophagy the transforming growth factor (TGF)-β/Smad4 pathway.

Methods: miR-34a expression levels were detected in CRC tissues and CRC cell lines by quantitative real-time polymerase chain reaction. Computational search, functional luciferase assay and western blotting were used to demonstrate the downstream target of miR-34a in CRC cells. Cell viability was measured with Cell Counting Kit-8. Apoptosis and macroautophagy of CRC cells were analyzed by flow cytometry and transmission electron microscopy, and expression of beclin I and LC3-II was detected by western blotting.

Results: Expression of miR-34a was significantly reduced while expression of TGF-β and Smad4 was increased in CRC patients treated with OXA-based chemotherapy. OXA treatment also resulted in decreased miR-34a levels and increased TGF-β and Smad4 levels in both parental cells and the OXA-resistant CRC cells. Activation of macroautophagy contributed to OXA resistance in CRC cells. Expression levels of Smad4 and miR-34a in CRC patients had a significant inverse correlation and overexpressing miR-34a inhibited macroautophagy activation by directly targeting Smad4 through the TGF-β/Smad4 pathway. OXA-induced downregulation of miR-34a and increased drug resistance by activating macroautophagy in CRC cells.

Conclusion: miR-34a mediates OXA resistance of CRC by inhibiting macroautophagy the TGF-β/Smad4 pathway.

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