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.
Bibliographical noteFunding Information:
This work was supported by the NIH [grant K08GM089941 (awarded to R.S. Huang), R21 CA139278 (awarded to R.S. Huang), UO1GM61393 (awarded to M.J. Ratain)]; University of Chicago Support Grant (#P30 CA14599; awarded to M. LeBeau); Breast Cancer SPORE Career Development Award (CA125183; awarded to R.S. Huang); the National Center for Advancing Translational Sciences of the NIH (UL1RR024999; awarded to J. Solway); Circle of Service Foundation Early Career Investigator award (awarded to R.S. Huang), and a Conquer Cancer Foundation of ASCO Translational Research Professorship award In Memory of Merrill J. Egorin, MD (awarded to M.J. Ratain). J.T.-H. Chang received support from the Biological Sciences Collegiate Division Research Endowments at the University of Chicago.