Downregulation of miR-491-5p promotes gastric cancer metastasis by regulating SNAIL and FGFR4.

ABSTRACT: Gastric cancer (GC) is among the most fatal cancers in China. MicroRNAs (miRNAs) are versatile regulators during GC development and progression. miR-491-5p has been demonstrated to act as a tumor suppressor in several types of cancer. However, the role of miR-491-5p in GC metastasis remains unknown. Here, we found that miR-491-5p was significantly decreased in GC tissues compared with adjacent non-cancerous tissues, and low miR-491-5p level was associated with large tumor size. Overexpression of miR-491-5p significantly suppressed GC cell epithelial-to-mesenchymal transition (EMT) and tumor metastasis in vitro and in vivo. Mechanistically, SNAIL was identified as a direct target of miR-491-5p. The silencing of SNAIL phenocopied the tumor suppressive function of miR-491-5p, whereas re-expression of SNAIL in GC cells rescued the EMT markers and cell migratory ability that were inhibited by miR-491-5p. In addition, miR-491-5p inhibited FGFR4 indirectly. Inhibition of FGFR4 also decreased the SNAIL level and impaired EMT and cell migration. Taken together, these findings indicate that downregulation of miR-491-5p promoted GC metastasis by inducing EMT via regulation of SNAIL and FGFR4.

SUBMITTER: Yu T 

PROVIDER: S-EPMC5980274 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature