MiR-625-5p Modulates the Metastasis and Proliferation of Gastric Cancer Cells by Governing the M6A Demethylase ALKBH5

Abstract

Background: Gastric cancer is a prevalent malignant tumor globally, with metastasis and recurrence serving as primary contributors to the diminished survival rates observed in patients with advanced stages of the disease. Despite numerous investigations into the pathogenesis of gastric cancer, the significance of m6A demethylase ALKBH5 in the initiation and progression of the disease has been established, yet its precise mechanism remains incompletely understood. Methods: Immunohistochemistry was utilized for the evaluation of ALKBH5 expression in gastric cancer tissues, while RT-qPCR and WB were employed for the analysis of ALKBH5 expression in cells. Additionally, the levels of m6A methylation in RNA were assessed using the EpiQuikTM m6A methylation quantitative assay kit. The proliferative and metastatic potentials of gastric cancer cells were assessed using the CCK-8 and Transwell cell assays, respectively. The binding site between miR-625-5p and ALKBH5 was predicted through the TargetScan website, and the interaction was confirmed using a dual luciferase reporter assay. Results: The research findings indicated a significant increase in m6A methylation levels in gastric cancer cells, concomitant with a substantial decrease in ALKBH5 expression. ALKBH5 can inhibit the proliferation and metastasis of gastric cancer cells. Additionally, the interaction between miR- 625-5p and the 3'-UTR of ALKBH5 mRNA, resulting in the suppression of ALKBH5 expression, was validated. Conclusions: Through its specific interaction with ALKBH5, miR-625-5p modulates the proliferation and metastatic potential of gastric cancer cells, bridging a previously unexplored link in the pathogenesis of gastric cancer between miR-625-5p and ALKBH5. This finding suggests that miR- 625-5p could be a potential target for treating gastric cancer, with the goal of enhancing patient outcomes and quality of life.