title: miR-133a suppresses ovarian cancer cell proliferation by directly targeting insulin-like growth factor 1 receptor.
abstract: The microRNA miR-133a is dysregulated in many types of cancer, but the underlying mechanism remains largely unknown. In this study, we showed that the expression level of miR-133a was reduced in ovarian cancer tissues compared with normal ovaries. Ectopic expression of miR-133a significantly inhibited ovarian cancer cell proliferation and colony formation, and induced G1-phase cell cycle arrest, whereas decreased miR-133a expression dramatically enhanced cell proliferation and colony formation. Importantly, miR-133a overexpression suppressed in vivo tumor growth in nude mice models. Through in silico search, we found that the 3'-untranslated region (UTR) of insulin-like growth factor 1 receptor (IGF1R) contains an evolutionarily conserved miR-133a binding site. miR-133a overexpression repressed IGF1R-3'UTR reporter activity, and reduced the mRNA and protein levels of endogenous IGF1R. Rescue experiments showed that ectopic expression of IGF1R significantly promoted the proliferation of ovarian cancer cells stably overexpressing miR-133a. Taken together, these findings indicate that miR-133a is an important regulator in ovarian cancer, and that its suppressive effects are mediated by targeting IGF1R.
authors.affiliation: Department of Gynecology, The Affiliated Tumor Hospital of Harbin Medical University, 150 Haping Road, Nan Gang District, Harbin, 150081, Heilongjiang Province, China.
authors.forename: Jinling
authors.initials: J
authors.lastname: Guo
authors.forename: Bairong
authors.initials: B
authors.lastname: Xia
authors.forename: Fanling
authors.initials: F
authors.lastname: Meng
authors.forename: Ge
authors.initials: G
authors.lastname: Lou
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D017451:Receptors, Somatomedin / Q000096:biosynthesis / Q000235:genetics*; D013002:Somatomedins / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; C548234:MIRN133 microRNA, human; D035683:MicroRNAs; D017451:Receptors, Somatomedin; D013002:Somatomedins