Case Control Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 7, 2020; 26(13): 1474-1489
Published online Apr 7, 2020. doi: 10.3748/wjg.v26.i13.1474
Effects of long non-coding RNA Opa-interacting protein 5 antisense RNA 1 on colon cancer cell resistance to oxaliplatin and its regulation of microRNA-137
Jing Liang, Xiao-Feng Tian, Wei Yang
Jing Liang, Department of Gastrointestinal Surgery, China-Japan Union Hospital of Jilin University, Changchun 130000, Jilin Province, China
Xiao-Feng Tian, Wei Yang, Department of Hepatopancreatobiliary Surgery, China-Japan Union Hospital of Jilin University, Changchun 130000, Jilin Province, China
Author contributions: Yang W performed the majority of experiments and analyzed the data; Liang J performed the molecular investigations; Tian XF and Yang W designed and coordinated the research, and wrote the paper.
Institutional review board statement: This study was reviewed and approved by the China-Japan Union Hospital of Jilin University Ethics Committee.
Informed consent statement: All patients in our study provided informed consent.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
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: Wei Yang, MD, Chief Physician, Department of Hepatopancreatobiliary Surgery, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Avenue, Changchun 130000, Jilin Province, China. 18345893430@163.com
Received: December 4, 2019
Peer-review started: December 4, 2019
First decision: January 16, 2020
Revised: February 4, 2020
Accepted: March 9, 2020
Article in press: March 9, 2020
Published online: April 7, 2020
Abstract
BACKGROUND

The incidence of colon cancer (CC) is currently high, and is mainly treated with chemotherapy. Oxaliplatin (L-OHP) is a commonly used drug in chemotherapy; however, long-term use can induce drug resistance and seriously affect the prognosis of patients. Therefore, this study investigated the mechanism of Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) on L-OHP resistance by determining the expression of OIP5-AS1 and microRNA-137 (miR-137) in CC cells and the effects on L-OHP resistance, with the goal of identifying new targets for the treatment of CC.

AIM

To study the effects of long non-coding RNA OIP5-AS1 on L-OHP resistance in CC cell lines and its regulation of miR-137.

METHODS

A total of 114 CC patients admitted to China-Japan Union Hospital of Jilin University were enrolled, and the expression of miR-137 and OIP5-AS1 in tumor tissues and corresponding normal tumor-adjacent tissues was determined. The influence of OIP5-AS1 and miR-137 on the biological behavior of CC cells was evaluated. Resistance to L-OHP was induced in CC cells, and their activity was determined and evaluated using cell counting kit-8. Flow cytometry was used to analyze the apoptosis rate, Western blot to determine the levels of apoptosis-related proteins, and dual luciferase reporter assay combined with RNA-binding protein immunoprecipitation to analyze the relationship between OIP5-AS1 and miR-137.

RESULTS

OIP5-AS1 was up-regulated in CC tissues and cells, while miR-137 was down-regulated in CC tissues and cells. OIP5-AS1 was inversely correlated with miR-137 (P < 0.001). Silencing OIP5-AS1 expression significantly hindered the proliferation, invasion and migration abilities of CC cells and markedly increased the apoptosis rate. Up-regulation of miR-137 expression also suppressed these abilities in CC cells and increased the apoptosis rate. Moreover, silencing OIP5-AS1 and up-regulating miR-137 expression significantly intensified growth inhibition of drug-resistant CC cells and improved the sensitivity of CC cells to L-OHP. OIP5-AS1 targetedly inhibited miR-137 expression, and silencing OIP5-AS1 reversed the resistance of CC cells to L-OHP by promoting the expression of miR-137.

CONCLUSION

Highly expressed in CC, OIP5-AS1 can affect the biological behavior of CC cells, and can also regulate the resistance of CC cells to L-OHP by mediating miR-137 expression.

Keywords: Long non-coding RNA Opa-interacting protein 5 antisense RNA 1, MicroRNA-137, Colon cancer, Drug resistance, Oxaliplatin, Biological behavior

Core tip: Long non-coding RNA (lncRNA) has drug resistance in various diseases, which has become a research hotspot, and it can participate in the regulation of various biological functions in cells. In this study, the expression and regulation mechanism of lncRNA Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) in colon cancer were investigated, and it was found that OIP5-AS1 was up-regulated in colon cancer cells. Dual luciferase reporter gene and RNA-binding protein immunoprecipitation assays were carried out, and the relationship between microRNA-137 and OIP5-AS1 was determined. The results showed that OIP5-AS1 could mediate drug resistance to oxaliplatin in these cells by regulating microRNA-137.