Abstract
Methyl-CpG-binding protein 2 (MECP2), an epigenetic regulatory factor, promotes the carcinogenesis and progression of a number of cancers. However, its role in the migration and invasion of gastric cancer (GC), as well as the underlying molecular mechanisms, remain unclear. In this study, we found that MECP2 promoted the migration, invasion and metastasis of GC cells. Investigation of the molecular mechanism revealed that MECP2 repressed F-box and WD40 domain protein 7 (FBXW7) transcription in GC by binding to the methylated CpG sites in the FBXW7 promoter region. MECP2 expression was markedly negatively correlated with the FBXW7 level in GC tissues. FBXW7 expression was significantly downregulated in GC tissues and cell lines, and low FBXW7 expression was correlated with unfavorable clinicopathologic features. FBXW7 inhibited cell migration and invasion by regulating the Notch1/c-Myc/mTOR signaling pathways, and knockdown of FBXW7 reversed the effects of silencing MECP2. Moreover, MECP2 upregulated the Notch1/c-Myc/mTOR signaling pathways by inhibiting FBXW7 expression at the transcriptional level. This study demonstrates that MECP2 promotes the migration and invasion of GC cells by modulating the Notch1/c-Myc/mTOR signaling pathways via suppression of FBXW7 transcription. These findings suggest that MECP2 may be a novel effective therapeutic target in GC.