oa Characterization Of Circular Rnas In Ovarian Cancer

Noncoding RNAs such as ribosomal RNAs (rRNA), transfer RNAs (tRNA) micro RNAs (miRNA), small interfering RNAs (siRNA) and long noncoding RNAs (lncRNA) are the dominant products of eukaryotic transcription and collectively represent more than 95% of total RNA of the cell. In addition to contributing as the core components of the translational machinery (rRNAs and tRNAs), these noncoding RNAs have been shown to be involved in a myriad of biological processes such as gene expression regulation and genome defence. Recently, a novel class of endogenously encoded species of RNA called circular RNAs (circRNA) has been shown to regulate gene expression in mammals by competing with miRNA targets under diverse scenarios. To investigate the role and regulatory potency of circRNAs in ovarian cancer, we performed paired-end RNA sequencing of 9 ovarian cancer samples from three patients at primary and metastatic stages and developed an in-house computational pipeline to identify and characterize the circRNA candidates. Our results show that circRNAs are widely expressed in ovarian cancer and oncogenic factors in cancer-associated pathways are particularly enriched for circRNAs. We also show that isoform diversity of circRNAs is comparable to that of the linear counterparts and a significant fraction of exons are preferentially expressed as circular forms compared to the canonical linear RNA form. Further, these candidate circRNAs are particularly enriched for miRNA seed matches and the hybridization energies of interaction favourably predicts formation of stable structural dimers between circRNAs and miRNA mature sequences. A large number of candidate circRNAs are also differentially expressed between primary and metastatic stages of ovarian cancer and show co-expression with their gene targets, implying a role for circRNAs in regulating expression of oncogenic factors. Taken together this study adds an important new dimension to the role of miRNAs vis-à-vis circRNAs in fine-tuning of gene expression and disease progression in ovarian cancer.