DNMT1 promotes the proliferation and migration of gastric cancer cells by inducing microRNA-125a-5p methylation to promote SERPINE1 protein  

作　　者：Hui Xie Hui Wang Ru-Hong Li Yue-Wen Zhang Xi-Rui Fan Xiao-Xue He Ao-Ran Guan 

机构地区：[1]Department of General Surgery,Yan’an Hospital of Kunming City,Kunming 650051,Yunnan Province,China [2]Department of Digestive Internal Medicine,Yan’an Hospital of Kunming City,Kunming 650051,Yunnan Province,China

出　　处：《World Journal of Gastrointestinal Oncology》2025年第3期188-201,共14页世界胃肠肿瘤学杂志(英文)

基　　金：the Research Program of the Science and Technology Department of Yunnan Province,No.202101AY070001-204.

摘　　要：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.

关 键 词：Gastric cancer microRNA-125a-5p DNA methyltransferase 1 SERPINE1 METHYLATION 

分 类 号：R735.2[医药卫生—肿瘤]