Mechanism of growth inhibition by MicroRNA 145: the role of the IGF-I receptor signaling pathway.
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.
La Rocca
Gaspare
G
Department of Cancer Biology at Thomas Jefferson University, Kimmel Cancer Center, Philadelphia, PA 19107, USA.
Badin
Margherita
M
Shi
Bin
B
Xu
Shi-Qiong
SQ
Deangelis
Tiziana
T
Sepp-Lorenzinoi
Laura
L
Baserga
Renato
R
D020413:3' Untranslated Regions; D016475:3T3 Cells; D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D020413:3' Untranslated Regions; D055504:Insulin Receptor Substrate Proteins; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D017526:Receptor, IGF Type 1