Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Aug 15, 2023; 15(8): 1384-1399
Published online Aug 15, 2023. doi: 10.4251/wjgo.v15.i8.1384
Antitumor activity of miR-188-3p in gastric cancer is achieved by targeting CBL expression and inactivating the AKT/mTOR signaling
Jian-Jiao Lin, Bao-Hua Luo, Tao Su, Qiong Yang, Qin-Fei Zhang, Wei-Yu Dai, Yan Liu, Li Xiang
Jian-Jiao Lin, Tao Su, Qin-Fei Zhang, Yan Liu, Li Xiang, Department of Gastroenterology, The Second Affiliated Hospital of Chinese University of Hong Kong (Shenzhen Longgang District People's Hospital), Shenzhen 518172, Guangdong Province, China
Bao-Hua Luo, Department of Urology, Hospital of Southern University of Science and Technology, Shenzhen 518055, Guangdong Province, China
Qiong Yang, Department of Gastroenterology, The Second Affiliated Hospital of the University of South China, Hengyang 421001, Hunan Province, China
Wei-Yu Dai, Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Author contributions: All authors contributed significantly to this work, whether in the conception, study design, execution, acquisition of data, analysis, and interpretation or in all these areas; Specifically, Lin JJ, Luo BH, and Xiang L designed and conceived the study. Su T, Yang Q performed in vitro experiments, Dai WY conducted in vitro experiments, and Zhang QF helped with data analysis; Liu Y and Lin JJ wrote the manuscript; All authors read and approved the final version of this manuscript.
Supported by the National Natural Science Funds of China, No. 81974448; Guangdong Medical Research Foundation, No. B2019126; and Shenzhen Science and Technology Innovation Commission, No. JCYJ20210324135005013.
Institutional review board statement: This study protocols were by the Institutional Ethical Standards Committee of Nanfang Hospital (#NFEC-2019-010), Southern Medical University (Guangzhou, China). All experiments were performed in accordance with the relevant guidelines and regulations.
Informed consent statement: Informed consent statement was waived due to the retrospective nature of the study.
Institutional animal care and use committee statement: All animal procedures were reviewed and approved by the Experimental Animal Ethics Committee of The Second Affiliated Hospital of the Chinese University of Hong Kong, Shenzhen (Longgang District People's Hospital).
Conflict-of-interest statement: There is no conflict of interest in this study.
Data sharing statement: The datasets generated and analyzed during the present study are available from the corresponding author upon reasonable request.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Li Xiang, PhD, Doctor, Department of Gastroenterology, The Second Affiliated Hospital of Chinese University of Hong Kong (Shenzhen Longgang District People's Hospital), No. 53 Aixin Road, Shenzhen 518172, Guangdong Province, China.shellyxiangli@163.com
Received: March 30, 2023
Peer-review started: March 30, 2023
First decision: April 25, 2023
Revised: May 29, 2023
Accepted: July 7, 2023
Article in press: July 7, 2023
Published online: August 15, 2023
ARTICLE HIGHLIGHTS
Research background

Altered miR-188-3p expression has been observed in various human cancers, while report of its role in gastric cancer needs further investigation.

Research motivation

Better understanding of miR-188-3p biology, functions, and molecular mechanism of action in gastric cancer could lead to develop novel strategies in control gastric cancer.

Research objectives

This study assessed miR-188-3p expression and functions in gastric cancer tissues and cells, respectively.

Research methods

Gastric cancer and normal tissues were obtained to detect miR-188-3p expression using quantitative reverse transcriptase-polymerase chain reaction and cell lines were used to manipulate miR-188-3p expression and functions in vitro using different assays. After that, miR-188-3p regulation of CBL expression was predicted bioinformatically and confirmed using a luciferase gene reporter assay. The Kaplan-Meier analysis was used to associate miR-188-3p or CBL expression with survival of gastric cancer patients. After that, we performed a nude mouse tumor cell xenograft assay to confirm the in vitro and ex vivo data.

Research results

miR-188-3p expression was low in plasma from gastric cancer patients, tissues, and cell lines compared to controls. Downregulated miR-188-3p expression was associated with clinicopathological data from patients. Furthermore, the ex vivo, in vitro, and in vivo data confirmed miR-188-3p directly targeted CBL, while overexpression of miR-188-3p inhibited CBL autophagy through the AKT/mTOR signaling pathway to promote the proliferation of gastric cancer.

Research conclusions

The current data provides ex vivo, in vitro, and in vivo evidence showing that miR-188-3p acts as a tumor suppressor gene or at least possesses antitumor activity in gastric cancer.

Research perspectives

These findings provide a novel insight into the molecular mechanism underlying gastric cancer development and progression and may offer a novel approach in control of this disease in future.