Clinically relevant microRNAs in ovarian cancer

Abstract

microRNAs (miRNAs/miRs) belong to a class of small noncoding RNAs that can negatively regulate messenger RNA (mRNA) expression of target genes. miRNAs are involved inmultiple aspects of ovarian cancer cell dysfunction and the phenotype of ovarian cancer cells can be modified by targeting miRNA expression. miRNA profiling has detected a number of candidate miRNAs with the potential to regulatemanyimportant biologic functions in ovarian cancer, but their role still needs to be clarified, given the remarkable heterogeneity among ovarian cancers and the contextdependent role of miRNAs. This review summarizes the data collected fromTheCancer Genome Atlas (TCGA) and several other genome-wide projects to identify dysregulated miRNAs in ovarian cancers. Copy number variations (CNVs), epigenetic alterations, and oncogenic mutations are also discussed that affect miRNA levels in ovarian disease. Emphasis is given to the role of particular miRNAs in altering expression of genes in human ovarian cancers with the potential to provide diagnostic, prognostic, and therapeutic targets. Particular attention has been given to TP53, BRCA1/ 2, CA125 (MUC16), HE4 (WFDC2), and imprinted genes such as ARHI (DIRAS3). A better understanding of the abnormalities in miRNA expression and downstream transcriptional and biologic consequences will provide leads for more effective biomarkers and translational approaches in the management of ovarian.