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): 1366-1383
Published online Aug 15, 2023. doi: 10.4251/wjgo.v15.i8.1366
LINC01268 promotes epithelial-mesenchymal transition, invasion and metastasis of gastric cancer via the PI3K/Akt signaling pathway and targeting MARCKS
Ling-Han Tang, Peng-Cheng Ye, Lin Yao, Ya-Jun Luo, Wang Tan, Wan-Ping Xiang, Zi-Lin Liu, Ling Tan, Jiang-Wei Xiao
Ling-Han Tang, Zi-Lin Liu, Jiang-Wei Xiao, Department of Gastrointestinal Surgery, Clinical Medical College and the First Affiliated Hospital of Chengdu Medical College, Chengdu 610000, Sichuan Province, China
Peng-Cheng Ye, Lin Yao, Department of Gastrointestinal Surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
Ya-Jun Luo, Department of Gastrointestinal Surgery, Sichuan Cancer Hospital, Chengdu 610000, Sichuan Province, China
Wang Tan, Department of Gastrointestinal Surgery, Yaan People’s Hospital, Yaan 625000, Sichuan Province, China
Wan-Ping Xiang, Department of Thoracic Surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
Ling Tan, Department of Surgery, People’s Hospital Affiliated to Chongqing Three Gorges Medical College, Chongqing 404041, China
Author contributions: Tang LH and Xiao JW conceived and designed the experiments; Tang LH and Ye PC did most of the experiments and data analysis; Tang LH wrote the manuscript; Ye PC, Luo YJ, Yao L and Liu ZL collected the clinical data; Tan W, Xiang WP and Tan L performed data analysis; Xiao JW revised the manuscript; and all authors have read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 81070378 and 81270561; and Natural Science Foundation of Sichuan Province, China, No. 2022NSFSC0050 and 2023NSFSC1896.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of the Affiliated Hospital of North Sichuan Medical College.
Informed consent statement: All gastric cancer patients and healthy volunteers provided written informed consent.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: Jiang-Wei Xiao, MD, PhD, Doctor, Professor, Surgeon, Department of Gastrointestinal Surgery, Clinical Medical College and the First Affiliated Hospital of Chengdu Medical College, No. 278 Baoguang Road, Xindu District, Chengdu 610000, Sichuan Province, China. xiaojiangwei2018@163.com
Received: February 12, 2023
Peer-review started: February 12, 2023
First decision: March 28, 2023
Revised: April 11, 2023
Accepted: June 19, 2023
Article in press: June 19, 2023
Published online: August 15, 2023
Processing time: 178 Days and 23.8 Hours
ARTICLE HIGHLIGHTS
Research background

Long non-coding RNAs (lncRNAs) are a class of RNA molecules with a length of more than 200 nucleotides. It plays an important role in many life activities such as epigenetic regulation, cell cycle regulation, and cell differentiation regulation. More and more studies have found that lncRNAs also affect the occurrence and development of tumors. LncRNAs have also been found to be involved in the regulation of gastric cancer (GC) progression, which may open up new directions for the diagnosis and treatment of GC.

Research motivation

GC is still a malignant tumor of digestive system with high incidence rate and mortality worldwide. Although many lncRNAs related to GC have been discovered in recent years, our understanding of their mechanisms of action is not yet deep enough. Exploring more GC associated lncRNAs and delving into the underlying mechanisms will help us learn more about the development and progression of GC, and hopefully improve the early screening rate and cure rate of GC.

Research objectives

The main objective of this study is to investigate the impact of high expression of LINC01268 in GC on the diagnosis and prognosis evaluation of GC patients, and to explore the impact and mechanism of LINC01268 on the biological behavior of GC cells in vitro experiments. Our study found that GC patients with high expression of LINC01268 have poor prognosis. High expression of LINC01268 can activate the MARCKS and PI3K/Akt signaling pathway, promoting the invasion, metastasis, and epithelial-mesenchymal transition (EMT) processes of GC cells. These may provide potential directions for targeted therapeutic drugs for GC.

Research methods

Real-time quantitative polymerase chain reaction was used to detect the expression of LINC01268 in GC. The receiver operating characteristic curve and Kaplan-Meier method were used for the analysis of the diagnostic value and prognostic evaluation of LINC01268 in patients with GC. Transwell assays and wound healing assays were used to confirm the effect of LINC01268 on the invasion and migration of GC cells. The regulatory relationship between LINC01268 and MARCKS, the PI3K/Akt signaling pathway, and the EMT process in GC was demonstrated by western blot analysis.

Research results

Our study found that high expression of LINC01268 was associated with some pathological features of GC patients and was predictive of poor prognosis. In vitro experiments, after knocking down LINC01268, the invasion and metastasis ability of MGC80-3 and AGS decreased. Meanwhile, molecular mechanism studies have found that LINC01268 may regulate the MARCKS, PI3K/Akt signaling pathway, and EMT process in GC cells.

Research conclusions

LINC01268 may promote GC invasion and metastasis by activating MARCKS, PI3K/Akt signaling pathway, and promoting EMT process. High expression of LINC01268 contributed to the poor prognosis of GC patients.

Research perspectives

The present study provides a promising direction for targeted therapy of GC. Animal experiments and more comprehensive molecular biology experiments would be better to confirm our conclusions, which is also the direction of our future research.