Publication Synopsis

MicroRNA expression and identification of putative miRNA targets in ovarian cancer

In order to better define the clinical and biological features of ovarian cancer, researchers from Johns Hopkins Medical Institutions and National Institute of Aging, Baltimore, Maryland, USA, and the Norwegian Radium Hospital, Oslo, Norway identified microRNA expression profiles in human ovarian cancer tissues and cell lines. Using microRNA arrays they identified over 80 differentially expressed miRNAs in ovarian cancer tissues and cell lines including miR_221 (highly up-regulated), miR-21 (down-regulated) and several members of the let-7 family (down-regulated). IPA analysis of the experimentally identified targets of deregulated miRNA identified cancer-relevant pathways and processes commonly targeted by these miRNAs, and also highlighted that the specific molecular pathways targeted by microRNA deregulation are likely tissue and cell-line dependent. Follow up studies elucidating the interactions between these miRNAs, their targets, and the pathways they regulate will serve to identify better markers of ovarian cancer and novel points for therapeutic intervention.

In order to experimentally identify the downstream targets of miRNAs deregulated in ovarian cancer, the research team transfected miR-98, miR-34c, miR 424 and let-7f in two different ovarian cancer cell lines BG-1 and UCI-101. They then measured mRNAs that changed in response to the transfected miRNA. These experimentally identified targets were analyzed in IPA to understand the molecular functions, cellular phenotypes and cancer-related pathways predicted to be affected by deregulated miRNA expression in ovarian cancer. IPA Functional Analysis identified functions such as cellular movement, cell cycle and cardiovascular functions to be consistently affected across the two ovarian cancer cell lines. Interestingly, with the exception of Integrin Signaling, the signaling pathways identified by IPA as associated with mRNA targets from each cell line were not consistent; suggesting that miRNA target selection and therefore miRNA function is likely tissue dependent.