Due to its high expression level in GC and its critical function in driving GC progression, MeCP2 represents a promising therapeutic target for GC treatment.
Univariate and multivariate analyses showed that gender, histological type, lymph node metastasis, and MECP2 expression were independent prognostic factors of GC.The dysregulated expression of MECP2 in GC and its correlation to clinicopathological parameters indicate that MECP2 may regulate the development of GC.
Examination of the TCGA Gastric Cancer databases demonstrated that nine glycogenes (24.6%) were oppositely regulated by MeCP2 in MeCP2 knockdown BGC-823 cells relative to their expression level in GC tissues, and might be downstream genes of MeCP2.
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.
Altogether, our results indicate that MECP2 promote the proliferation of GC cells via miR-338 (miR-338-3p and miR-338-5p)-mediated antitumor and gene regulatory effect.