Abstract
Methyl-CpG binding protein 2 (MeCP2) is involved in the carcinogenesis and progression of multiple types of cancer. However, its precise role in gastric cancer (GC) and the relevant molecular mechanism remain unknown. In the present study, we found that miR-638 levels were lower in GC tissues and GC cell lines than in adjacent normal tissues and normal gastric epithelial cell lines, respectively. Low miR-638 levels were associated with poor tumor differentiation, tumor size and lymph node metastasis. MeCP2 expression levels were higher in GC tissues than in adjacent normal tissues. It was found that miR-638 inhibited GC cell proliferation, colony formation, G1-S transition and tumor growth, and induced cell apoptosis by directly targeting MeCP2. MeCP2 promoted GC cell proliferation, colony formation and G1-S cell-cycle transition, and suppressed apoptosis. Molecular mechanistic investigations were performed using an integrated approach with a combination of microarray analysis, chromatin immunoprecipitation sequencing and a reporter gene assay. The results showed that MeCP2 bound to the methylated CpG islands of G-protein-coupled receptor kinase-interacting protein 1 (GIT1) promoter and upregulated its expression, thereby activating the MEK1/2-ERK1/2 signaling pathway and promoting GC cell proliferation. Taken together, our study demonstrates that MeCP2, a target of miR-638, facilitates GC cell proliferation and induces cell-cycle progression through activation of the MEK1/2-ERK1/2 signaling pathway by upregulating GIT1. The findings suggest that MeCP2 plays a significant role in GC progression, and may serve as a potential target for GC therapy.