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Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051202 | PMC |
| http://dx.doi.org/10.1002/cam4.1605 | DOI Listing |
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