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Mechanism of growth inhibition by MicroRNA 145: The role of the IGF‐I receptor signaling pathway
Author(s) -
La Rocca Gaspare,
Badin Margherita,
Shi Bin,
Xu ShiQiong,
DeAngelis Tiziana,
SeppLorenzinoi Laura,
Baserga Renato
Publication year - 2009
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21796
Subject(s) - microrna , suppressor , insulin like growth factor receptor , colorectal cancer , receptor , insulin like growth factor , cell growth , untranslated region , signal transduction , growth factor , mechanism (biology) , cancer research , cancer cell , biology , growth factor receptor , downregulation and upregulation , chemistry , irs1 , cancer , microbiology and biotechnology , insulin receptor , endocrinology , messenger rna , insulin , gene , biochemistry , genetics , insulin resistance , philosophy , epistemology
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.