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

Authors: Shi B; Sepp-Lorenzino L; Prisco M; Linsley P; deAngelis T; Baserga R

Abstract: 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.

Keywords: Base Sequence; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms/genetics/*metabolism/*pathology; Down-Regulation; Gene Expression Regulation, Neoplastic; Genes, Reporter/genetics; Humans; Insulin Receptor Substrate Proteins; MicroRNAs/*genetics; Phosphoproteins/*genetics/*metabolism; RNA, Messenger/genetics
Journal: The Journal of biological chemistry
Volume: 282
Issue: 45
Pages: 32582-90
Date: Sept. 11, 2007
PMID: 17827156
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Citation:

Shi B, Sepp-Lorenzino L, Prisco M, Linsley P, deAngelis T, Baserga R (2007) Micro RNA 145 targets the insulin receptor substrate-1 and inhibits the growth of colon cancer cells. The Journal of biological chemistry 282: 32582-90.


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