Snail-Modulated MicroRNA 493 Forms a Negative Feedback Loop with the Insulin-Like Growth Factor 1 Receptor Pathway and Blocks Tumorigenesis.

摘要: In this study, we have identified one microRNA, microRNA 493 (miR-493), which could simultaneously and directly regulate multiple genes downstream of the insulin-like growth factor 1 receptor (IGF1R) pathway, including IGF1R, by binding with complementary sequences in 3' untranslated region (UTR) mRNAs insulin substrate (IRS1), mitogen-activated protein kinase (MAPK1), thereby potentiating their inhibitory function at levels development progression cancers. This was further confirmed pulldown miR AGO-2 antibody. Further, results from head neck samples showed that miR-493 were significantly downregulated tumors, a concomitant increase expression IGF1R key effectors. Functional studies overexpression cells nude-mouse models revealed tumor suppressor functions miR-493. Regulation Snail binds to promoter represses it. We found existence dynamic negative feedback loop regulation mediated via Snail. Our study nicotine treatment decreases miR-493-with Snail-an indication toward tumorigenesis, reestablishing role tobacco as major risk for cancers elucidating mechanism behind nicotine-mediated tumorigenesis.