Mechanism of growth inhibition by MicroRNA 145: The role of the IGF-I receptor signaling pathway
Article first published online: 23 APR 2009
Copyright © 2009 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 220, Issue 2, pages 485–491, August 2009
How to Cite
La Rocca, G., Badin, M., Shi, B., Xu, S.-Q., DeAngelis, T., Sepp-Lorenzinoi, L. and Baserga, R. (2009), Mechanism of growth inhibition by MicroRNA 145: The role of the IGF-I receptor signaling pathway. J. Cell. Physiol., 220: 485–491. doi: 10.1002/jcp.21796
- Issue published online: 26 MAY 2009
- Article first published online: 23 APR 2009
- Manuscript Accepted: 19 MAR 2009
- Manuscript Received: 18 MAR 2009
- National Institutes of Health. Grant Number: CA 089640
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. J. Cell. Physiol. 220: 485–491, 2009. © 2009 Wiley-Liss, Inc.