title: MiR-373 targeting of the Rab22a oncogene suppresses tumor invasion and metastasis in ovarian cancer.
abstract: Metastasis is major cause of mortality in patients with ovarian cancer. MiR-373 has been shown to play pivotal roles in tumorigenesis and metastasis; however, a role for miR-373 in ovarian cancer has not been investigated. In this study, we show that the miR-373 expression is down-regulated in human epithelial ovarian cancer (EOC) and inversely correlated with clinical stage and histological grade. Ectopic overexpression of miR-373 in human EOC cells suppressed cell invasion in vitro and metastasis in vivo, and the epithelial-mesenchymal transition process. Silencing the expression of miR-373 resulted in an increased migration and invasion of EOC cells. Using integrated bioinformatics analysis, gene expression arrays, and luciferase assay, we identified Rab22a as a direct and functional target of miR-373 in EOC cells. Expression levels of miR-373 were inversely correlated with Rab22a protein levels in human EOC tissues. Rab22a knockdown inhibited invasion and migration of EOC cells, increased E-cadherin expression, and suppressed the expression of N-cadherin. Moreover, overexpression of Rab22a abrogated miR-373-induced invasion and migration of EOC cells. Taken together, these results demonstrate that miR-373 suppresses EOC invasion and metastasis by directly targeting Rab22a gene, a new potential therapeutic target in EOC.
authors.affiliation: Department of Obstetrics and Gynecology, RenJi Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Key Laboratory of Gynecologic Oncology, Shanghai, 200127, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Urology, Shanghai First People's Hospital, Shanghai Jiao-Tong University, Shanghai, 200080, China.
authors.forename: Fu-Jun
authors.initials: FJ
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics and Gynecology, RenJi Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Key Laboratory of Gynecologic Oncology, Shanghai, 200127, China.
authors.forename: Li-Lan
authors.initials: LL
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, RenJi Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Key Laboratory of Gynecologic Oncology, Shanghai, 200127, China.
authors.forename: Luo-Qiao
authors.initials: LQ
authors.lastname: Wang
authors.affiliation: Medical Sciences, Indiana University School of Medicine, Bloomington, IN 47405, USA.
authors.forename: Kenneth P
authors.initials: KP
authors.lastname: Nephew
authors.affiliation: Department of Pathophysiology, Chemical Biology Division of Shanghai Universities E-Institutes, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Ying-Li
authors.initials: YL
authors.lastname: Wu
authors.affiliation: Department of Obstetrics and Gynecology, RenJi Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Key Laboratory of Gynecologic Oncology, Shanghai, 200127, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000818:Animals; D015153:Blotting, Western; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D020691:rab GTP-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C527114:MIRN373 microRNA, human; D035683:MicroRNAs; C484191:RAB22A protein, human; D020691:rab GTP-Binding Proteins