title: Mechanism of growth inhibition by MicroRNA 145: the role of the IGF-I receptor signaling pathway.
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.
authors.affiliation: Department of Cancer Biology at Thomas Jefferson University, Kimmel Cancer Center, Philadelphia, PA 19107, USA.
authors.forename: Gaspare
authors.initials: G
authors.lastname: La Rocca
authors.forename: Margherita
authors.initials: M
authors.lastname: Badin
authors.forename: Bin
authors.initials: B
authors.lastname: Shi
authors.forename: Shi-Qiong
authors.initials: SQ
authors.lastname: Xu
authors.forename: Tiziana
authors.initials: T
authors.lastname: Deangelis
authors.forename: Laura
authors.initials: L
authors.lastname: Sepp-Lorenzinoi
authors.forename: Renato
authors.initials: R
authors.lastname: Baserga
mesh_terms: 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*
chemical_list: D020413:3' Untranslated Regions; D055504:Insulin Receptor Substrate Proteins; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D017526:Receptor, IGF Type 1