title: MicroRNAs 125a and 125b inhibit ovarian cancer cells through post-transcriptional inactivation of EIF4EBP1.
abstract: The aim of the present study was to identify the specific miRNAs involved in regulation of EIF4EBP1 expression in ovarian cancer and to define their biological function. miRNA mimics and miRNA inhibitors were used in quantitative PCR, western blotting, and luciferase reporter assays to assess cell migration, invasiveness, and viability. miR-125a and miR-125b were downregulated in ovarian cancer tissue and cell lines relative to healthy controls. Increased expression of miR-125a and miR-125b inhibited invasion and migration of SKOV3 and OVCAR-429 ovarian cancer cells and was associated with a decrease in EIF4EBP1 expression. The inverse relationship between miR-125a and miR-125b was corroborated by cotransfection of a luciferase reporter plasmid. Furthermore, miR-125a and miR-125b caused apoptosis and decreased cell viability and migration in an apparently EIF4EBP1-directed manner. Collectively, these results indicate that miR-125a and miR-125b are important posttranscriptional regulators of EIF4EBP1 expression, providing rationale for new therapeutic approaches to suppress tumour invasion and migration using miR-125a, miR-125b, or their mimics for the treatment of ovarian cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Maria
authors.initials: M
authors.lastname: Lee
authors.affiliation: Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Eun Jae
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Myung Jae
authors.initials: MJ
authors.lastname: Jeon
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D015153:Blotting, Western; D016022:Case-Control Studies; D018797:Cell Cycle Proteins; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D035683:MicroRNAs / Q000235:genetics*; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D010750:Phosphoproteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering
keywords: EIF4EBP1; epithelial ovarian cancer; microRNA; microRNA 125a; microRNA 125b