Mechanism of Growth Inhibition by MicroRNA 145: The Role of the IGF-I Receptor Signaling Pathway

MicroRNA 145(miR14S) has been proposed as a tumor suppressor. It was previously shown that miR145 targets the 3' UTR of the insulin receptor substrate-I (IRS-I) and dramatically inhibits the growth of colon cancer cells. milk 145 also targets the type I insulin-like growth factor receptor (IGF-IR). We show here that an IRS-I lacking its 3' UTR is no longer down-regulated by milk 145 and rescues colon cancer cells from miR 145-induced inhibition of growth. An IGF-IR resistant to milk 145 (again by elimination of its 3' UTR) is not down-regulated by milk 145 but fails to rescue colon cancer cells from growth inhibition. These and other results, taken together, indicate that down-regulation of IRS-I plays a significant role in the tumor suppressor activity of milk 145. J. Cell. Physiol. 220: 485-491, 2009. (C) 2009 Wiley-Liss, Inc.