Micro RNA 145 targets the insulin receptor substrate-1 and inhibits the growth of colon cancer cells
Document Type
Article
Publication Date
November 2007
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.
Recommended Citation
Shi, Bin; Sepp-Lorenzino, Laura; Prisco, Marco; Linsley, Peter; deAngelis, Tiziana; and Baserga, Renato, "Micro RNA 145 targets the insulin receptor substrate-1 and inhibits the growth of colon cancer cells" (2007). Department of Cancer Biology Faculty Papers. Paper 14.
https://jdc.jefferson.edu/cbfp/14
Supplemental data
Comments
This article has been peer reviewed. It is the authors' final version prior to publication in the Journal of Biological Chemistry 282(45):32582-32590, November 9, 2007. The published version is available at http://www.jbc.org/cgi/content/full/282/45/32582; copyright © by The American Society for Biochemistry and Molecular Biology, Inc.