Abstract 3485: Identification and characterization of circular RNAs in cancer

Abstract

Abstract Circular RNAs (circRNAs) are an abundant class of non-coding RNAs that are formed by a backsplice event resulting in formation of covalently closed circular RNA molecules. The efficiency of backsplicing is inferior to linear splicing, however, due to their long half-lives circRNAs can accumulate to high levels in cells. Functional characterization of a few circRNAs has shown that they can act as endogenous microRNA sponges and transcriptional regulators; one example is CDR1as/ciRS-7, which has been shown to act as a sponge for miR-7. However, the functions of most circRNAs are still unknown. To study the potential role of circRNAs in cancer, we identified exonic circRNA candidates by analysing ENCODE RNAseq data from a panel of cancer cell lines. We used chimeric alignment detection implemented in the STAR aligner and subsequent filtering of output files to identify chimeric alignments consistent with circRNA backsplice sites. The circular nature of the identified putative circRNAs was validated by testing their resistance to RNase R digestion, and sequences surrounding the backsplice sites were used as target recognition sequences for designing LNA-modified gapmer antisense oligonucleotides (ASOs) to specifically knock down the circular isoforms of the RNA transcripts. Data from ongoing studies on knockdown of several abundant circRNAs in cancer cell lines, assessment of the specificity of backsplice-targeting ASOs relative to the linear mRNA counterparts, and analyses to identify biological effects of modulating circRNA levels in cultured cells will be presented. Citation Format: Charlotte A. Thrue, Andreas Petri, Marianne B. Løvendorf, Karen Dybkær, Dimitrios Papaioannou, Ramiro Garzon, Sakari Kauppinen. Identification and characterization of circular RNAs in cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3485. doi:10.1158/1538-7445.AM2017-3485