Theranostics 2017; 7(13):3338-3353. doi:10.7150/thno.20512 This issue
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.