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miR-625 reverses multidrug resistance in gastric cancer cells by directly targeting ALDH1A1

Authors Gong X, Xu B, Zi L, Chen X

Received 14 March 2019

Accepted for publication 28 May 2019

Published 15 July 2019 Volume 2019:11 Pages 6615—6624

DOI https://doi.org/10.2147/CMAR.S208708

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 5

Editor who approved publication: Professor Nakshatri


Xufei Gong, Baoli Xu, Li Zi, Xinrui Chen

Department of General Surgery, Linyi People’s Hospital, Linyi, Shandong 276002, People’s Republic of China

Background: microRNAs (miRNAs) are emerging as critical regulators of multidrug resistance (MDR) in gastric cancer, a major cause of chemotherapy failure. miR-625 is downregulated in gastric cancer and negatively associated with metastasis. In the current study, we aimed to investigate whether miR-625 regulates MDR in gastric cancer.
Methods: The level of miR-625 in gastric cancer cells with or without MDR was quantified by quantitative reverse transcription PCR (qRT-PCR) analysis. The sensitivity of gastric cancer cells to chemotherapeutic agents was assessed by MTT assay. The protein expression was determined by Western blot analysis, and the luciferase reporter assay was applied to confirm miR-625 regulation of the potential target.
Results: miR-625 is downregulated in MDR gastric cancer cells compared with chemosensitive counterparts. In addition, miR-625 increases the sensitivity and promotes apoptosis of gastric cancer cells when treated with different chemotherapeutic agents. Moreover, miR-625 directly targets the aldehyde dehydrogenase 1A1 (ALDH1A1), and importantly, the restoration of ALDH1A1 expression rescues miR-625 effects on MDR in gastric cancer cells.
Conclusion: miR-625 reverses MDR in gastric cancer cells by targeting ALDH1A1. Hence, our study identifies miR-625 as a novel regulator of MDR in gastric cancer cells, and implicates its potential application for overcoming MDR in gastric cancer chemotherapy.

Keywords: miR-625, multidrug resistance, gastric cancer, ALDH1A1, apoptosis
 

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