Micro RNA 145 targets the insulin receptor substrate-1 and inhibits the growth of colon cancer cells

The insulin receptor substrate- 1 ( IRS- 1), a docking protein for both the type 1 insulin- like growth factor receptor ( IGF- IR) and the insulin receptor, is known to send a mitogenic, anti- apoptotic, and anti- differentiation signal. Several micro RNAs ( miRs) are suggested by the data base as possible candidates for targeting IRS- 1. We show here that one of the miRs predicted by the data base, miR145, whether transfected as a synthetic oligonucleotide or expressed from a plasmid, causes down- regulation of IRS- 1 in human colon cancer cells. IRS- 1 mRNA is not decreased by miR145, while it is down- regulated by an siRNA targeting IRS- 1. Targeting of the IRS- 1 3'-untranslated region (UTR) by miR145 was confirmed using a reporter gene ( luciferase) expressing the miR145 binding sites of the IRS- 1 3'-UTR. In agreement with the role of IRS- 1 in cell proliferation, we show that treatment of human colon cancer cells with miR145 causes growth arrest comparable to the use of an siRNA against IRS- 1. Taken together, these results identify miR145 as a micro RNA that down- regulates the IRS- 1 protein, and inhibits the growth of human cancer cells.