Theranostics 2017; 7(13):3338-3353. doi:10.7150/thno.20512
MicroRNA-647 Targets SRF-MYH9 Axis to Suppress Invasion and Metastasis of Gastric Cancer
1. Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangdong Provincial Engineering Technology Research Center of Minimally Invasive Surgery, Guangzhou, 510515 China;
2. Guangdong Key Laboratory of Laboratory Animal, Guangdong Laboratory Animal Monitoring Institute, Guangzhou 510663, China;
3. Leder Human Biology and Translational Medicine, Biology and Biomedical Sciences, Division of Medical Sciences, Harvard Medical School, Boston, MA 02115.
* These authors contributed equally to this work
† Present address: Department of General Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, 361003 China.
‡ Present address: Department of General Surgery, Panyu Central Hospital, Guangzhou, 511400 China
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, Metastasis, MicroRNA-647, MYH9, SRF.
Ye G, Huang K, Yu J, Zhao L, Zhu X, Yang Q, Li W, Jiang Y, Zhuang B, Liu H, Shen Z, Wang D, Yan L, Zhang L, Zhou H, Hu Y, Deng H, Liu H, Li G, Qi X. MicroRNA-647 Targets SRF-MYH9 Axis to Suppress Invasion and Metastasis of Gastric Cancer. Theranostics 2017; 7(13):3338-3353. doi:10.7150/thno.20512. Available from http://www.thno.org/v07p3338.htm