MicroRNA-647 Targets SRF-MYH9 Axis to Suppress Invasion and Metastasis of Gastric Cancer

Abstract

MicroRNAs (miRNAs) play important roles in regulating tumour development and progression. Here we show that miR-647 is repressed in gastric cancer (GC), and associated with GC metastasis. Moreover, we identify that miR-647 can suppress GC cell migration and invasion in vitro. Mechanistically, we confirm miR-647 directly binds to the 3' untranslated regions of SRF mRNA, and SRF binds to the CArG box located at the MYH9 promoter. CCG-1423, an inhibitor of RhoA/SRF-mediated gene transcription, inhibits the expression of MYH9, especially in SRF downregulated cells. Overexpression of miR-647 inhibits MGC 80-3 cells' metastasis in orthotropic GC models, but increasing SRF expression in these cells reverses this change. Importantly, we found the synergistic inhibition effect of CCG-1423 and agomir-647, an engineered miRNA mimic, on cancer metastasis in orthotropic GC models. Our study demonstrates that miR-647 functions as a tumor metastasis suppressor in GC by targeting SRF/MYH9 axis.

Keywords: Gastric cancer; MYH9; Metastasis; MicroRNA-647; SRF..