title: miR-494 suppresses tumor growth of epithelial ovarian carcinoma by targeting IGF1R.
abstract: A growing body of evidence suggests that microRNA-494 (miR-494) could act as tumor-suppressive or oncogenic microRNAs (miRNAs) in different types of tumors. However, the biological roles and underlying mechanisms of miR-494 remain unknown in human epithelial ovarian carcinoma (EOC). Therefore, the aims of this study were to investigate the miR-494 expression and the significance of its clinical diagnosis in patients suffering EOC and to analyze its role and underlying molecular mechanism on the carcinogenesis of EOC. Here, we found that miR-494 was significantly decreased in EOC cell lines and tissues and its expression was negatively correlated with advanced International Federation of Gynecology and Obstetrics (FIGO) stage, high pathological grade, and lymph node metastasis (all P < 0.01). Functional studies showed that overexpression of miR-494 in EOC cells could remarkably inhibit proliferation, colony formation, migration, and invasion and induce cell apoptosis, G0/G1 phase arrest. An in vivo analysis revealed that the overexpression of miR-494 suppressed tumor growth in a nude mouse xenograft model system. Bioinformatic assay and dual-luciferase assay confirmed that insulin-like growth factor 1 receptor (IGF1R) was as a direct target of miR-494 in EOC cells. Western blot assay showed that overexpression of miR-494 inhibited IGF1R expression and its downstream signal protein expression. In addition, downregulation of IGF1R has similar effects with miR-494 overexpression on EOC cells and overexpression of IGF1R effectively rescued the inhibition of overexpressed miR-494 in EOC cells. These data suggested that miR-494 functions as a tumor suppressor in EOC by targeting IGF1R.
authors.affiliation: Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Changchun, 130021, Jilin Province, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Changchun, 130021, Jilin Province, People's Republic of China.
authors.forename: Xiaosu
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics and Gynecology, The Second Hospital of Jilin University, Changchun, 130041, Jilin Province, People's Republic of China.
authors.forename: Lufei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Changchun, 130021, Jilin Province, People's Republic of China.
authors.forename: Shi
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, The Second Hospital of Jilin University, Changchun, 130041, Jilin Province, People's Republic of China. cuimanhua1326@163.com.
authors.forename: Manhua
authors.initials: M
authors.lastname: Cui
authors.affiliation: Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Changchun, 130021, Jilin Province, People's Republic of China. hejin506b@sohu.com.
authors.forename: Jin
authors.initials: J
authors.lastname: He
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D002277:Carcinoma / Q000235:genetics / Q000473:pathology*; D002455:Cell Division; D002460:Cell Line; D002465:Cell Movement; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D064593:Heterografts; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D010053:Ovary / Q000166:cytology; D012334:RNA, Neoplasm / Q000235:genetics*; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics; D014410:Tumor Stem Cell Assay
chemical_list: D020413:3' Untranslated Regions; C000597236:IGF1R protein, human; C547168:MIRN494 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D017451:Receptors, Somatomedin; D017526:Receptor, IGF Type 1
keywords: Epithelial ovarian carcinoma; IGF1R; MicroRNAs; miR-494