The role of Dysregulated Microrna in Ovarian Cancer

Abstract

Ovarian cancer is the most lethal gynaecological malignancy and the sixth most common cause of cancer death in Australian women. Epithelial ovarian cancer accounts for 90% of ovarian cancers, of which, serous epithelial ovarian cancer is the most common and aggressive histological subtype. MicroRNAs (miRNAs) are a class of small non-coding RNA molecules that negatively regulate genes involved in cancer. Genomic instability is a hallmark of ovarian cancer which may be exacerbated by DNA hypomethylation. The role of aberrant methylation and copy number variation (CNV) on miRNA dysregulation was assessed by qPCR methylation arrays and integrative analysis of cytogenetic arrays, miRNA expression and gene expression profiles. Several miRNAs identified to be adjacent to CpG islands aberrantly methylated or located in regions of CNV. Of these, the mir-23a/mir-24-2/mir-27a cluster and mir-425 were identified to be in regions of CNV and were predicted to target oncogenic receptor tyrosine kinases AXL and MET. Furthermore, one of the unmet needs for ovarian cancer patient survival is reliable detection. Current diagnostic tests for ovarian cancer may be improved by expansion of biomarker panels such as circulating miRNAs. Assessment of miRNA expression profiles identified the miR-200 family to be over-expressed in ovarian cancer patient serum