Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 14, 2021; 27(6): 487-500
Published online Feb 14, 2021. doi: 10.3748/wjg.v27.i6.487
Circular RNA circVAPA promotes chemotherapy drug resistance in gastric cancer progression by regulating miR-125b-5p/STAT3 axis
Peng Deng, Ming Sun, Wen-Yan Zhao, Bin Hou, Kai Li, Tao Zhang, Feng Gu
Peng Deng, Bin Hou, Kai Li, Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
Ming Sun, Department of Urology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
Wen-Yan Zhao, Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
Tao Zhang, Department of Stem Cells and Regenerative Medicine, China Medical University, Shenyang 110122, Liaoning Province, China
Feng Gu, Department of Ophthalmology, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
Author contributions: Deng P and Sun M performed the majority of experiments and analyzed the data; Zhao WY performed the molecular investigations; Hou B and Gu F designed and coordinated the research; Li K and Zhang T wrote the paper.
Supported by Natural Science Foundation of Liaoning Province, No. 2019-MS-385.
Institutional review board statement: This study was reviewed and approved by the First Affiliated Hospital of China Medical University.
Institutional animal care and use committee statement: The animal study was reviewed and approved by the First Affiliated Hospital of China Medical University.
Conflict-of-interest statement: The authors declare no conflict of interest related to this manuscript.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Feng Gu, PhD, Chief Physician, Department of Ophthalmology, The First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Heping District, Shenyang 110001, Liaoning Province, China. fenggu78186069@163.com
Received: December 6, 2020
Peer-review started: December 6, 2020
First decision: December 17, 2020
Revised: December 21, 2020
Accepted: January 7, 2021
Article in press: January 7, 2021
Published online: February 14, 2021
Processing time: 60 Days and 21.3 Hours
ARTICLE HIGHLIGHTS
Research background

Gastric cancer (GC) is a common malignant tumor and causes a high incidence of cancer-associated death. Cisplatin (DDP)-based chemotherapy is the main therapy for clinical GC treatment, but the mechanism of chemotherapy resistance is still poorly understood, which is a severe clinical challenge. CircRNAs have been identified to play a vital role in regulating the chemoresistance of gastric cancer cells. The development process of GC chemotherapy resistance is not well-understood. In addition, it is well known that circRNAs and miRNAs are involved in chemotherapy resistance of GC cells. However, the role of circVAPA and miR-125b-5p in regulating the chemotherapy resistance of GC cells has not been reported yet.

Research motivation

To investigate the impact of circVAPA on chemotherapy resistance during the progression of GC.

Research objectives

We collected the clinical GC tissue samples (n = 50) and the adjacent normal tissues (n = 50) and analyzed the effect of circVAPA on GC progression and chemotherapy resistance.

Research methods

The role of circVAPA in chemotherapy resistance and GC progression was analyzed by transwell assay, MTT assay, colony formation assay, healing assay, and wound flow cytometry analysis in GC cells and DDP resistant GC cell lines, and in vivo tumorigenicity analysis in nude mice. The mechanism was investigated by quantitative real-time PCR, luciferase reporter assay, and Western blot analysis.

Research results

CircVAPA depletion inhibited proliferation, migration, and invasion and increased apoptosis of GC cells. CircVAPA knockdown reduced tumor growth of GC cells in vivo. CircVAPA promoted the chemotherapy resistance of GC cells. We found that circVAPA targeted miR-125b-5p and miR-125b-5p to STAT3 in GC cells. MiR-125b-5p inhibitor rescued the depletion of circVAPA and enhanced the inhibitory effect of DDP on GC cells, while STAT3 knockdown prevented the proliferation of DDP-treated SGC7901/DDP cells induced by circVAPA overexpression. Depletion of STAT3 and miR-125b-5p inhibitor reversed circVAPA depletion-induced GC cell apoptosis.

Research conclusions

CircVAPA promotes chemotherapy resistance and the malignant progression of GC cells by modulating miR-125b-5p/STAT3 signaling. CircVAPA and miR-125b-5p may be considered as potential targets for GC therapy.

Research perspectives

CircRNA circVAPA promotes chemotherapy drug resistance in the progression of gastric cancer by regulating the miR-125b-5p/STAT3 axis.