title: miR-17 inhibits ovarian cancer cell peritoneal metastasis by targeting ITGA5 and ITGB1.
abstract: An essential step in the peritoneal spread of ovarian cancer is the adhesion and implantation of tumor cells to the mesothelium layer. Integrin α5 and β1 have been reported to mediate the initial adhesion process and to correlate with disease survival in ovarian cancer. However, the molecular mechanism of integrin α5β1 dysregulation in tumorigenesis and metastasis remained enigmatic. In the present study, using the US NCI60 database, we identified miR-17 as a candidate regulator targeting both integrin α5 and β1. The level of miR-17 was evidently inversely correlated with that of α5 and β1 in ovarian cancer cell lines. Specifically, miR-17 bound directly to the 3' untranslated region (3'UTR) of α5 and β1 and suppressed their expression. Forced expression of miR-17 led to markedly diminished adhesion and invasion of ovarian cancer cells in vitro, and notably reduced metastatic nodules inside the peritoneal cavity in in vivo SKOV3 xenografts model. Moreover, ectopic expression of miR-17 in ovarian cancer cells resulted in repressed ILK phosphorylation as well as decreased production of active matrix metalloproteinase-2 (MMP-2). Our results indicated that miR-17 hampered ovarian cancer peritoneal propagation by targeting integrin α5 and β1. These findings supported the utility of miR-17/α5β1 to be considered as valuable marker for metastatic potential of ovarian cancer cells, or a therapeutic target in ovarian cancer treatment.
authors: Department of Obsterics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430010, P.R. China.
authors: Cheng
authors: C
authors: Gong
authors: Department of Obsterics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430010, P.R. China.
authors: Zongyuan
authors: Z
authors: Yang
authors: Department of Medicinal Chemistry, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, P.R. China.
authors: Fenghua
authors: F
authors: Wu
authors: Department of Medicinal Chemistry, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, P.R. China.
authors: Lintao
authors: L
authors: Han
authors: Department of Obsterics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430010, P.R. China.
authors: Yi
authors: Y
authors: Liu
authors: Department of Oncology, XiangYang Central Hospital, Hubei University of Arts and Science, XiangYang, Hubei 441021, P.R. China.
authors: Wei
authors: W
authors: Gong
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039564:Integrin alphaV / Q000096:biosynthesis* / Q000235:genetics; D019012:Integrin beta1 / Q000096:biosynthesis* / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary; D023041:Xenograft Model Antitumor Assays
chemical_list: D039564:Integrin alphaV; D019012:Integrin beta1; C524941:MIRN17 microRNA, human; D035683:MicroRNAs; D020778:Matrix Metalloproteinase 2