title: High Expression of miR-532-5p, a Tumor Suppressor, Leads to Better Prognosis in Ovarian Cancer Both In Vivo and In Vitro.
abstract: Ovarian cancer is the leading cause of death for gynecologic cancers, ranking fifth overall for cancer-related death among women. The identification of biomarkers and the elucidation of molecular mechanisms for improving treatment options have received extensive efforts in ovarian cancer research. miRNAs have high potential to act as both ovarian cancer biomarkers and as critical regulators of ovarian tumor behavior. We comprehensively analyzed global mRNA, miRNA expression, and survival data for ovarian cancer from The Cancer Genome Atlas (TCGA) to pinpoint miRNAs that play critical roles in ovarian cancer survival through their effect on mRNA expression. We performed miRNA overexpression and gene knockdown experiments to confirm mechanisms predicted in our bioinformatics approach. We established that overexpression of miR-532-5p in OVCAR-3 cells resulted in a significant decrease in cell viability over a 96-hour time period. In the TCGA ovarian cancer dataset, we found 67 genes whose expression levels were negatively correlated with miR-532-5p expression and correlated with patient survival, such as WNT9A, CSNK2A2, CHD4, and SH3PXD2A The potential miR-532-5p-regulated gene targets were found to be enriched in the Wnt pathway. Overexpression of miR-532-5p through miRNA mimic caused downregulation of CSNK2A2, CHD4, and SH3PXD2A in the OVCAR-3 cell line. We have discovered and validated the tumor-suppressing capabilities of miR-532-5p both in vivo through TCGA analysis and in vitro through ovarian cancer cell lines. Our work highlights the potential clinical importance of miR-532-5p expression in ovarian cancer patients. Mol Cancer Ther; 15(5); 1123-31. ©2016 AACR.
authors.affiliation: Department of Medicine, University of Chicago, Chicago, Illinois.
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.affiliation: Biological Sciences Collegiate Division, University of Chicago, Chicago, Illinois.
authors.forename: Jeremy T-H
authors.initials: JT
authors.lastname: Chang
authors.affiliation: Pritzker School of Medicine, University of Chicago, Chicago, Illinois.
authors.forename: Chester Jingshiu
authors.initials: CJ
authors.lastname: Kao
authors.affiliation: Department of Medicine, University of Chicago, Chicago, Illinois. rhuang@medicine.bsd.uchicago.edu.
authors.forename: R Stephanie
authors.initials: RS
authors.lastname: Huang
mesh_terms: D001324:Autoantigens / Q000235:genetics; D014408:Biomarkers, Tumor; D047390:Casein Kinase II / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006801:Humans; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality*; D011379:Prognosis; D059467:Transcriptome
chemical_list: D001324:Autoantigens; D014408:Biomarkers, Tumor; C115323:CHD4 protein, human; C585583:MIRN532 microRNA, human; D035683:MicroRNAs; C570325:CSNK2A1 protein, human; D047390:Casein Kinase II; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex