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

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.