Epigenetic silencing of miR‐1271 enhances MEK1 and TEAD4 expression in gastric cancer

Abstract

Abstract Epigenetic dysregulation is a major driver of tumorigenesis. To identify tumor‐suppressive microRNAs repressed by DNA methylation in gastric cancer (GC), we analyzed the genome‐wide DNA methylation and microRNA expression profiles of EpCAM+/CD44+ GC cells. Among the set of microRNAs screened, miR‐1271 was identified as a microRNA repressed by DNA methylation in GC. Forced miR‐1271 expression substantially suppressed the growth, migration, and invasion of GC cells. To identify candidate target genes and signaling pathways regulated by miR‐1271, we performed RNA sequencing. Among the genes down‐regulated by miR‐1271, MAP2K1 (MEK1) was significantly repressed by miR‐1271, and the associated ERK/MAPK signaling pathway was also inhibited. TEAD4 was also repressed by miR‐1271, and the associated YAP1 signatures within genes regulated by miR‐1271 were significantly enriched. These findings uncovered MEK1 and TEAD4 as novel miR‐1271 targets and suggest that the epigenetic silencing of miR‐1271 is crucial for GC development.

Keywords

• DNA methylation
• gastric cancer
• MEK1
• miR‐1271
• TEAD4