Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jul 15, 2023; 15(7): 1182-1199
Published online Jul 15, 2023. doi: 10.4251/wjgo.v15.i7.1182
ENTPD1-AS1–miR-144-3p-mediated high expression of COL5A2 correlates with poor prognosis and macrophage infiltration in gastric cancer
Han-Mei Yuan, Xiao-Feng Pu, Hui Wu, Chao Wu
Han-Mei Yuan, Hui Wu, Chao Wu, Department of Laboratory Medicine, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, Guangdong Province, China
Xiao-Feng Pu, Department of Clinical Laboratory, The General Hospital of Western Theater Command, Chengdu 610000, Sichuan Province, China
Author contributions: Yuan HM designed the experiments and wrote the manuscript; Pu XF and Wu H collected clinical specimens and completed the related experiments; Wu C reviewed and edited the manuscript; All authors contributed to the article and approved the submitted version.
Supported by National Natural Science Foundation of China, No. 81971489; and Natural Science Foundation of Guangdong Province, No. 2022A1515011122.
Institutional review board statement: The study was reviewed and approved by the Medical Research Ethics Committee of the Eighth Affiliated Hospital of Sun Yat-sen University, No. ZB-KYIRB-AF/SC-08/01.0.
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author.
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: Chao Wu, PhD, Professor, Department of Laboratory Medicine, The Eighth Affiliated Hospital, Sun Yat-sen University, No. 3025 Shennan Zhong Lu, Shenzhen 518033, Guangdong Province, China. chaowu261@163.com
Received: December 7, 2022
Peer-review started: December 7, 2022
First decision: January 18, 2023
Revised: March 30, 2023
Accepted: April 30, 2023
Article in press: April 30, 2023
Published online: July 15, 2023
ARTICLE HIGHLIGHTS
Research background

Gastric cancer (GC) is a malignant tumor with high morbidity and mortality. Expression of COL5A2 is significantly elevated in GC. However, its specific regulatory mechanism has not been elucidated.

Research motivation

Abnormal expression of noncoding RNAs (ncRNAs) has been found in GC, including microRNA (miRNA) and long noncoding RNA (lncRNA). The ncRNA regulatory mechanism and immune microenvironment related to COL5A2 in GC are not well understand.

Research objectives

To explore the competing endogenous RNA regulatory mechanism and immune mechanism of COL5A2 in GC.

Research methods

StarBase was used to predict the interaction of miRNA–lncRNA or miRNA–mRNA in GC. The direct interaction between COL5A2, miR-144-3p and ENTPD1-AS1 were verified by dual luciferase reporter assay. The correlation between of COL5A2 and macrophages infiltration was analyzed through bioinformatics and validated in paired GC tissues by immunohistochemical staining.

Research results

miR-144-3p interacted directly with COL5A2 and negatively regulated the expression of COL5A2. ENTPD1-AS1 was elevated in GC and competitively bound to miR-144-3p, thus inhibiting the expression of miR-144-3p. Compared to paired normal tissue, COL5A2 expression was upregulated at the protein level, especially in the middle and late stages of GC. The high expression of COL5A2 was positively linked to macrophage infiltration in GC.

Research conclusions

COL5A2 regulated by ENTPD1-AS1–miR-144-3p is associated with poor prognosis and macrophage infiltration in GC.

Research perspectives

ENTPD1-AS1-miR-144-3p-COL5A2 might be a new therapeutic target for GC.