Xie H, Wang H, Li RH, Zhang YW, Fan XR, He XX, Guan AR. DNMT1 promotes the proliferation and migration of gastric cancer cells by inducing microRNA-125a-5p methylation to promote SERPINE1 protein. World J Gastrointest Oncol 2025; 17(3): 98703 [DOI: 10.4251/wjgo.v17.i3.98703]
Corresponding Author of This Article
Ao-Ran Guan, Department of General Surgery, Yan’an Hospital of Kunming City, No. 245 Renmin East Road, Kunming 650051, Yunnan Province, China. guanaoran@126.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
Hui Xie, Ru-Hong Li, Yue-Wen Zhang, Ao-Ran Guan, Department of General Surgery, Yan’an Hospital of Kunming City, Kunming 650051, Yunnan Province, China
Hui Wang, Xi-Rui Fan, Xiao-Xue He, Department of Digestive Internal Medicine, Yan’an Hospital of Kunming City, Kunming 650051, Yunnan Province, China
Co-first authors: Hui Xie and Hui Wang.
Author contributions: Xie H and Wang H contributed equally to this work; Wang H contributed to visualization; Xie H contributed to validation; Xie H and Wang H contributed to conceptualization, project administration, writing original draft; Guan AR contributed to funding acquisition, investigation, resources, supervision, writing review and editing; Fan XR and He XX contributed to data curation and software; Li RH, Zhang YW contributed to formal analysis, and methodology; All authors have read and approved the final manuscript.
Supported by the Research Program of the Science and Technology Department of Yunnan Province, No. 202101AY070001-204.
Institutional review board statement: This study was conducted in accordance with the Declaration of Helsinki (as revised in 2013) and was approved by the Ethics Committee of Yan’an Hospital of Kunming City/Yan’an Hospital Affiliated to Kunming Medical University (No. 2020-078-01).
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
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: Ao-Ran Guan, Department of General Surgery, Yan’an Hospital of Kunming City, No. 245 Renmin East Road, Kunming 650051, Yunnan Province, China. guanaoran@126.com
Received: July 4, 2024 Revised: December 11, 2024 Accepted: December 23, 2024 Published online: March 15, 2025 Processing time: 225 Days and 7.7 Hours
Abstract
BACKGROUND
Gastric cancer (GC) is a malignant tumor originating from gastric mucosal epithelial cells that has high morbidity and mortality. microRNAs (miR) are important diagnostic markers and therapeutic targets in this disease.
AIM
To explore the mechanism of miR-125a-5p in the pathogenesis of GC.
METHODS
The expression levels of miR-125a-5p, SERPINE1 and DNMT1 in GC cells and tissues were detected by real-time polymerase chain reaction (PCR) and Western blotting. Methylation-specific PCR was used to detect the level of miR-125a-5p methylation. A cell counting kit 8 assay, scratch test, and a Transwell assay were performed to detect the proliferation, migration, and invasiveness of HGC27 cells, respectively. The expression of the epithelial mesenchymal transition (EMT)-related proteins E-cadherin, N-cadherin and vimentin in HGC27 cells was detected by Western blotting, while the expression of vimentin was detected by immunofluorescence.
RESULTS
This study revealed that miR-125a-5p was expressed at low levels in GC clinical samples and cells and that miR-125a-5p overexpression inhibited the proliferation, migration, invasiveness and EMT of GC cells. Mechanistically, miR-125a-5p can reduce GC cell proliferation, promote E-cadherin expression, inhibit N-cadherin and vimentin expression, and reduce the EMT of GC cells, thus constraining GC cells to a certain extent. Moreover, DNMT1 inhibited miR-125a-5p expression by increasing the methylation of the miR-125a-5p promoter, thereby promoting the expression of SERPINE1, which acts together with miR-125a-5p to exert antagonistic effects on GC.
CONCLUSION
Our study revealed that DNMT1 promoted SERPINE1 protein expression by inducing miR-125a-5p methylation, which led to the proliferation, migration and occurrence of EMT in GC cells.
Core Tip: This study revealed the tumor suppressive effect of microRNAs (miR)-125a-5p in gastric cancer (GC) through inhibition of cell proliferation, migration and invasion, and regulation of epithelial-mesenchymal transition related protein expression. The low expression of miR-125a-5p is associated with DNMT1-mediated promoter methylation and is negatively correlated with SERPINE1 expression. This discovery provides a new target for GC therapy.
