title: MicroRNA-133b inhibits proliferation and invasion of ovarian cancer cells through Akt and Erk1/2 inactivation by targeting epidermal growth factor receptor.
abstract: Aberrant expression of microRNA-133b (miR-133b) has been frequently reported in some cancers excluding ovarian cancer (OC). The role and its molecular mechanism of miR-133b in OC have not been reported. In this study, we explored the effects of miR-133b overexpression on proliferation and invasion in OC cells. The mRNA level of miR-133b in OC cell lines was determined by real-time PCR. The miR-133b mimic was transiently transfected into OC cells using Lipofectamine™ 2000 reagent. Subsequently, cell proliferation and invasion were assessed by MTT, Brdu-ELISA and Transwell assays. Moreover, the effects of miR-133b overexpression on the MAPK and PI3K/Akt signaling pathways were determined by Western blot. Protein level of EGFR was also measured by Western blotting. Meanwhile, luciferase assays were performed to validate EGFR as miR-133b target in OC cells. Our results showed that the mRNA level of miR-133b was remarkably decreased in OC cell lines compared with normal colon epithelium cells, whereas the protein expression of EGFR was significantly increased. Up-regulation of miR-133b inhibited the proliferation and invasion of OC cells. We also found that miR-133b overexpression evidently decreased the phosphorylation of Erk1/2 and Akt. Bioinformatics analysis predicted that the EGFR was a potential target gene of miR-133b. Luciferase reporter assay demonstrated that miR-133b could directly target EGFR. Altogether, our results indicated that miR-133b overexpression was shown to inhibit proliferation and invasion of OC cells through suppression of the MAPK and PI3K/Akt signaling pathways by targeting EGFR.
authors.affiliation: Department of Obstetrical, Shaanxi Provincial People's Hospital Xi'an 710068, Shaanxi Province, People's Republic of China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Tongchuan Mining Bureau Central Hospital Tongchuan 727000, Shaanxi Province, People's Republic of China.
authors.forename: Guohong
authors.initials: G
authors.lastname: Li
mesh_terms: D020413:3' Untranslated Regions; D001665:Binding Sites; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019295:Computational Biology; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; C548234:MIRN133 microRNA, human; D035683:MicroRNAs; C512478:EGFR protein, human; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: MAPK and PI3K/Akt signaling pathway; MicroRNA-133b; epidermal growth factor receptor; invasion; ovarian cancer; proliferation