ALKBH5-mediated m6A modification of circFOXP1 promotes gastric cancer progression by regulating SOX4 expression sponging miR-338-3p

Abstract

Abstract Circular RNAs (circRNAs) have recently been found as potential functional modulators of the cellular physiology processes in gastric cancer (GC). However, the potential clinical significance and molecular mechanisms of circRNAs involved in the development of GC remain largely unknown. In the study, we demonstrated that circFOXP1 was highly expressed in GC tissues compared with adjacent normal tissues. Higher circFOXP1 expression positively associated with tumor size, lymph node metastasis, TNM stage and poor prognosis in patients with GC. Multivariate Cox analysis revealed that higher circFOXP1 expression was an independent risk for the disease-free survival (DFS) and overall survival (OS) of GC patients. Functional studies showed that higher circFOXP1 expression promoted cell proliferation, cell invasion, and cell cycle progression in GC in vitro. In vivo, knockdown of circFOXP1 inhibited tumor growth. Mechanistically, by double luciferase reporter, Methylated RNA immunoprecipitation (MeRIP), RNA binding protein immunoprecipitation assay and RNA pull-down assays, we clarified that circFOXP1 was under m6A-modification mediated by ALKBH5 in GC cells. Besides, circFOXP1 promoted GC progression by regulating SOX4 expression sponging miR-338-3p in GC cells. In conclusion, our findings highlight that circFOXP1 could serve as a novel diagnostic and prognostic biomarker and potential therapeutic target of GC treatment.