title: Tumor suppressor role of miR-217 in human epithelial ovarian cancer by targeting IGF1R.
abstract: Accumulating evidence shows that microRNA-217 (miR-217) is frequently dysregulated in various cancers, and plays crucial roles in tumorigenesis and metastasis; however, the role and underlying molecular mechanism of miR-217 in human epithelial ovarian cancer (EOC) remains unclear. Here, we report that miR-217 expression was downregulated in EOC tissue and inversely correlated with advanced FIGO stage, high histological grading and lymph node metastasis (P<0.01). Function analysis revealed that the ectopic expression of miR-217 in EOC cells inhibited cell proliferation, migration and invasion in vitro, as well as suppressed tumor growth in vivo. Bioinformatics analysis and dual luciferase assays identified insulin-like growth factor 1 receptor (IGF1R) as a direct target of miR-217 in EOC cells. Western blot assay showed that overexpression of miR-217 in EOC cells inhibited IGF1R expression. In addition, downregulation of IGF1R mimicked the tumor-suppressive effects of miR-217 in EOC cells, whereas the reintroduction of IGF1R partially abrogated the suppression effect induced by miR-217 on EOC cells. Collectively, these results demonstrated that miR-217 plays a tumor suppressor role in human epithelial ovarian cancer by directly targeting IGF1R gene, suggesting a new potential therapeutic target in EOC.
authors.affiliation: Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, P.R. China.
authors.forename: Jieyan
authors.initials: J
authors.lastname: Li
authors.affiliation: Special Education Department of Changchun University, Changchun, Jilin 130022, P.R. China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Li
authors.affiliation: Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, P.R. China.
authors.forename: Weiyuan
authors.initials: W
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics*; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C000597236:IGF1R protein, human; C553315:MIRN217 microRNA, human; D035683:MicroRNAs; D017451:Receptors, Somatomedin; D017526:Receptor, IGF Type 1