Altered expression pattern of circular RNAs in primary and metastatic sites of epithelial ovarian carcinoma

// Ikhlak Ahmed 1 , Thasni Karedath 1 , Simeon S. Andrews 1 , Iman K. Al-Azwani 2 , Yasmin Ali Mohamoud 2 , Denis Querleu 3 , Arash Rafii 4 , Joel A. Malek 1, 2 1 Department of Genetic medicine, Weill Cornell Medicine-Qatar, Education City, Ar-Rayyan, Qatar 2 Genomics Core, Weill Cornell Medicine-Qatar, Education City, Ar-Rayyan, Qatar 3 Department of Gynecologic Oncology, Universite Montepllier 1, Montpellier, France 4 Stem Cell and Microenvironment Laboratory, Weill Cornell Medicine-Qatar, Education City, Ar-Rayyan, Qatar Correspondence to: Joel A. Malek, e-mail: jom2042@qatar-med.cornell.edu Keywords: circular RNA, ovarian cancer, peritoneal metastasis, lymph node metastasis, miRNA Received: December 07, 2015 Accepted: April 02, 2016 Published: April 22, 2016 ABSTRACT Recently, a class of endogenous species of RNA called circular RNA (circRNA) has been shown to regulate gene expression in mammals and their role in cellular function is just beginning to be understood. To investigate the role of circRNAs in ovarian cancer, we performed paired-end RNA sequencing of primary sites, peritoneal and lymph node metastases from three patients with stage IIIC ovarian cancer. We developed an in-house computational pipeline to identify and characterize the circRNA expression from paired-end RNA-Seq libraries. This pipeline revealed thousands of circular isoforms in Epithelial Ovarian Carcinoma (EOC). These circRNAs are enriched for potentially effective miRNA seed matches. A significantly larger number of circRNAs are differentially expressed between tumor sites than mRNAs. Circular and linear expression exhibits an inverse trend for many cancer related pathways and signaling pathways like NFkB, PI3k/AKT and TGF-β typically activated for mRNA in metastases are inhibited for circRNA expression. Further, circRNAs show a more robust expression pattern across patients than mRNA forms indicating their suitability as biomarkers in highly heterogeneous cancer transcriptomes. The consistency of circular RNA expression may offer new candidates for cancer treatment and prognosis.