Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Mar 15, 2024; 16(3): 1019-1028
Published online Mar 15, 2024. doi: 10.4251/wjgo.v16.i3.1019
Long non-coding RNA GATA6-AS1 is mediated by N6-methyladenosine methylation and inhibits the proliferation and metastasis of gastric cancer
Jun-Jie Shen, Min-Chang Li, Shao-Qi Tian, Wen-Ming Chen
Jun-Jie Shen, Department of Oncology, Jiangxi Hospital of Integrated Chinese and Western Medicine, Nanchang 330000, Jiangxi Province, China
Min-Chang Li, Department of Hepatopancreatobiliary Surgery, Jiangxi Hospital of Integrated Chinese and Western Medicine, Nanchang 330000, Jiangxi Province, China
Shao-Qi Tian, Clinical Medical School, Jining Medical University, Jining 272000, Shandong Province, China
Wen-Ming Chen, Department of Oncology, Jining No.1 People’s Hospital, Jining 272011, Shandong Province, China
Author contributions: Shen JJ performed the experiments, acquired and analyzed data, wrote the manuscript; Li MC performed the experiments; Tian SQ collected data; Chen WM designed and coordinated the study, wrote the manuscript; all authors approved the final version of the article.
Supported by Natural Science Foundation of Shandong Province, No. ZR2020MH207 and No. ZR2020MH251.
Conflict-of-interest statement: All authors have nothing to disclose.
Data sharing statement: No additional data are available.
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: Wen-Ming Chen, MD, Associate Chief Physician, Department of Oncology, Jining No.1 People’s Hospital, No. 6 Jiankang Road, Jining 272011, Shandong Province, China. yusuker9950529@163.com
Received: October 30, 2023
Peer-review started: October 30, 2023
First decision: December 6, 2023
Revised: December 16, 2023
Accepted: January 17, 2024
Article in press: January 17, 2024
Published online: March 15, 2024
Abstract
BACKGROUND

Through experimental research on the biological function of GATA6-AS1, it was confirmed that GATA6-AS1 can inhibit the proliferation, invasion, and migration of gastric cancer cells, suggesting that GATA6-AS1 plays a role as an anti-oncogene in the occurrence and development of gastric cancer. Further experiments confirmed that the overexpression of fat mass and obesity-associated protein (FTO) inhibited the expression of GATA6-AS1, thereby promoting the occurrence and development of gastric cancer.

AIM

To investigate the effects of GATA6-AS1 on the proliferation, invasion and migration of gastric cancer cells and its mechanism of action.

METHODS

We used bioinformatics methods to analyze the Cancer Genome Atlas (https://portal.gdc.cancer.gov/. The Cancer Genome Atlas) and download expression data for GATA6-AS1 in gastric cancer tissue and normal tissue. We also constructed a GATA6-AS1 lentivirus overexpression vector which was transfected into gastric cancer cells to investigate its effects on proliferation, migration and invasion, and thereby clarify the expression of GATA6-AS1 in gastric cancer and its biological role in the genesis and development of gastric cancer. Next, we used a database (http://starbase.sysu.edu.cn/starbase2/) to analysis GATA6-AS1 whether by m6A methylation modify regulation and predict the methyltransferases that may methylate GATA6-AS1. Furthermore, RNA immunoprecipitation experiments confirmed that GATA6-AS1 was able to bind to the m6A methylation modification enzyme. These data allowed us to clarify the ability of m6A methylase to influence the action of GATA6-AS1 and its role in the occurrence and development of gastric cancer.

RESULTS

Low expression levels of GATA6-AS1 were detected in gastric cancer. We also determined the effects of GATA6-AS1 overexpression on the biological function of gastric cancer cells. GATA6-AS1 had strong binding ability with the m6A demethylase FTO, which was expressed at high levels in gastric cancer and negatively correlated with the expression of GATA6-AS1. Following transfection with siRNA to knock down the expression of FTO, the expression levels of GATA6-AS1 were up-regulated. Finally, the proliferation, migration and invasion of gastric cancer cells were all inhibited following the knockdown of FTO expression.

CONCLUSION

During the occurrence and development of gastric cancer, the overexpression of FTO may inhibit the expression of GATA6-AS1, thus promoting the proliferation and metastasis of gastric cancer.

Keywords: Long non-coding RNA, GATA6-AS1, N6-methyladenine modification, Fat mass and obesity-associated protein, Gastric cancer

Core Tip: Long non-coding RNA GATA6-AS1 is down-regulated in gastric malignant tumor, and capable to inhibit the proliferation, migration and invasion of tumor cells, acting as a tumor suppressor gene in gastric cancer cells. Fat mass and obesity-associated protein (FTO) is highly expressed in gastric cancer, and the down-regulation of GATA6-AS1 in gastric cancer is regulated by the N6-methyladenine demethylase FTO. Therefore, during the occurrence and development of gastric cancer, overexpressed FTO may inhibit the expression of GATA6-AS1, thus promoting the proliferation and metastasis of gastric cancer.