Mechanism of growth inhibition by MicroRNA 145: the role of the IGF-I receptor signaling pathway.

Authors: La Rocca G; Badin M; Shi B; Xu SQ; Deangelis T; Sepp-Lorenzinoi L; Baserga R

Abstract: MicroRNA 145 (miR145) has been proposed as a tumor suppressor. It was previously shown that miR145 targets the 3' UTR of the insulin receptor substrate-1 (IRS-1) and dramatically inhibits the growth of colon cancer cells. miR145 also targets the type 1 insulin-like growth factor receptor (IGF-IR). We show here that an IRS-1 lacking its 3' UTR is no longer down-regulated by miR145 and rescues colon cancer cells from miR145-induced inhibition of growth. An IGF-IR resistant to miR145 (again by elimination of its 3' UTR) is not down-regulated by miR145 but fails to rescue colon cancer cells from growth inhibition. These and other results, taken together, indicate that down-regulation of IRS-1 plays a significant role in the tumor suppressor activity of miR145.

Keywords: 3' Untranslated Regions; 3T3 Cells; Active Transport, Cell Nucleus/physiology; Animals; Cell Line, Tumor; Colonic Neoplasms/genetics/metabolism/pathology; Gene Expression Regulation, Neoplastic; Humans; Insulin Receptor Substrate Proteins/genetics/*metabolism; Mice; MicroRNAs/genetics/*metabolism; Receptor, IGF Type 1/genetics/*metabolism; Signal Transduction/*physiology
Journal: Journal of cellular physiology
Volume: 220
Issue: 2
Pages: 485-91
Date: April 25, 2009
PMID: 19391107
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Citation:

La Rocca G, Badin M, Shi B, Xu SQ, Deangelis T, Sepp-Lorenzinoi L, Baserga R (2009) Mechanism of growth inhibition by MicroRNA 145: the role of the IGF-I receptor signaling pathway. Journal of cellular physiology 220: 485-91.


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