MicroRNA-145 regulates the proliferation, migration and invasion of human primary colon adenocarcinoma cells by targeting MAPK1.

ABSTRACT

Primary colon adenocarcinoma is responsible for high rates of mortality worldwide. The late diagnosis and lack of reliable biomarkers and therapeutic targets forms a bottleneck in the treatment of colon cancer. In the present study, the therapeutic potential of an important microRNA (miR), namely miR­145, was investigated in primary colon adenocarcinoma cells. The results revealed that the expression of miR­145 was significantly (P<0.05) downregulated in colon adenocarcinoma cells and the ectopic expression of miR­145 in colon cancer inhibited proliferation by promoting the apoptosis of SW480 primary colon adenocarcinoma cells. Furthermore, bioinformatics analysis revealed that miR­145 exerts its effected by targeting mitogen­activated protein kinase (MAPK) in SW480 cells. This was confirmed by expression analysis wherein the expression of MAPK1 was significantly (P<0.05) upregulated in the primary colon adenocarcinoma cells and the ectopic expression of miR­145 inhibited the expression of MAPK1. By contrast, the silencing of MAPK1 had similar effects on the proliferation, migration and invasion of SW480 cells as that of the overexpression of miR­145. Furthermore, it was observed that the inhibition of miR­145 did not reverse the effects of MAPK1 silencing on SW480 cells. However, the overexpression of MAPK1 led to considerable reversal of the effects of the overexpression of miR­145 on the proliferation, migration and invasion of SW480 cells. The effects of the overexpression of miR­145 were also evaluated in vivo in xenografted mice and it was observed that the overexpression of miR­145 also inhibited tumor growth and volume in vivo. Taken together, it was concluded that miR­145 may prove to be an important therapeutic target for colon cancer.