The role and mechanism of SOX4 in Helicobacter pylori-mediated gastric mucosal epithelial dysplasia
10.3969/j.issn.1006-7795.2025.04.010
- VernacularTitle:SOX4在幽门螺杆菌介导的胃黏膜上皮异型增生中的作用及机制研究
- Author:
Feng DU
1
;
Rui XU
;
Mengran ZHAO
;
Xu JI
;
Jiayi SU
;
Yuting QIU
;
Shengtao ZHU
;
Jing WU
;
Peng LI
;
Shutian ZHANG
Author Information
1. 首都医科大学附属北京友谊医院消化科 消化健康全国重点实验室 国家消化系统疾病临床医学研究中心 胃肠早癌药械研发北京市重点实验室,北京 100050
- Publication Type:Journal Article
- Keywords:
gastric cancer;
precancerous gastric lesions;
Helicobacter pylori;
SOX4;
MLH3;
transcriptional regulation
- From:
Journal of Capital Medical University
2025;46(4):644-653
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role and molecular mechanism of SOX4 in Helicobacter pylori(H.pylori)-mediated gastric mucosal epithelial dysplasia.Methods The expression of SOX4 in gastric tissues and cells was analyzed with reverse transcription-polymerase chain reaction(RT-PCR),Western blotting,and immunohistochemical staining.The effects of SOX4 on gastric epithelial cell proliferation and colony formation were determined with CCK-8 and colony formation assays.A PCR array was used to screen downstream target genes involved in H.pylori-induced dysplasia mediated by SOX4.The transcriptional regulation and binding sites of the target gene MLH3 by SOX4 were elucidated with luciferase reporter assay,promoter truncation assay,and chromatin immunoprecipitation(ChIP).Results SOX4 expression was significantly increased in H.pylori-infected gastric tissues(P<0.05).Overexpression of SOX4 markedly enhanced the proliferation and colony formation abilities of normal gastric epithelial cells(P<0.05).Elevated SOX4 led to the dysregulation of MLH3 and other DNA damage repair-related molecules after H.pylori infection in gastric epithelial cells(|logFC|>1,P<0.05).H.pylori promoted MLH3 expression in gastric epithelial cells through SOX4.SOX4 transcriptionally activated MLH3 expression by binding to the 5th site of the MLH3 promoter.The increased expression of SOX4 and MLH3 is associated with poor prognosis of gastric cancer patients.Conclusion SOX4 is closely associated with H.pylori-induced dysplasia in gastric epithelial cells.Upregulation of SOX4 promotes H.pylori-related dysplasia by transcriptionally activating MLH3,leading to the imbalance of proliferation and colony formation in gastric epithelial cells.
