MicroRNA-27b suppresses tumor progression by regulating ARFGEF1 and focal adhesion signaling.

ABSTRACT: The non-receptor tyrosine kinase c-Src is frequently activated during progression of colon cancers. In this study, we found that among the c-Src-regulated microRNAs (miRNAs), miR-27b is also repressed by activation of K-Ras/H-Ras. Inhibitor studies suggested that the phosphatidylinositol 3-kinase pathway is involved in the repression of miR-27b. MicroRNA-27b was repressed in various colon cancer cell lines and tumor tissues. Re-expression of miR-27b in human colon cancer HCT116 cells caused morphological changes and suppressed tumor growth, cell adhesion, and invasion. We also identified ARFGEF1 and paxillin as novel targets of miR-27b, and found that miR-27b-mediated regulation of ARFGEF1 is crucial for controlling anchorage-independent growth, and that of paxillin is important for controlling cell adhesion and invasion. Re-expression of miR-27b suppressed the activation of c-Src induced by integrin-mediated cell adhesion, suggesting that repression of miR-27b may contribute to c-Src activation in cancer cells. These findings show that miR-27b functions as a tumor suppressor by controlling ARFGEF1 and the paxillin/c-Src circuit at focal adhesions.

SUBMITTER: Matsuyama R 

PROVIDER: S-EPMC4724816 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature