Genome-wide identification of cancer-specific alternative splicing in circRNA

Abstract

Circular RNA (circRNA) is a group of RNA families generated by RNA circularization, which was discovered ubiquitously across different cancers. However, the internal structure of circRNA is difficult to determine due to alternative splicing that occurs in its exons and introns. Furthermore, cancer-specific alternative splicing of circRNA is less likely to be identified. Here, we proposed a de novo algorithm, CircSplice, that could identify internal alternative splicing in circRNA and compare differential circRNA splicing events between different conditions ( http://gb.whu.edu.cn/CircSplice or https://github.com/GeneFeng/CircSplice ). By applying CircSplice in clear cell renal cell carcinoma and bladder cancer, we detected 4498 and 2977 circRNA alternative splicing (circ-AS) events in the two datasets respectively and confirmed the expression of circ-AS events by RT-PCR. We further inspected the distributions and patterns of circ-AS in cancer and adjacent normal tissues. To further understand the potential functions of cancer-specific circ-AS, we classified those events into tumor suppressors and oncogenes and performed pathway enrichment analysis. This study is the first comprehensive view of cancer-specific circRNA alternative splicing, which could contribute significantly to regulation and functional research of circRNAs in cancers. Electronic supplementary material The online version of this article (10.1186/s12943-019-0996-0) contains supplementary material, which is available to authorized users.

circRNAs Are Involved in the Rice-Magnaporthe oryzae Interaction

“…Recent studies in mammals have shown the presence of very complex splice sites that generate splice junctions with more than two donors or acceptors Zhang et al, 2016;Feng et al, 2019;Zheng et al, 2019). We speculated complex splice sites should have a higher probability of successful back-splicing.…”

“…As a posttranscriptional process in eukaryotic organisms, alternative splicing leads to production of multiple, distinct functional transcripts and diverse proteins from a single gene (Black, 2000;Nilsen and Graveley, 2010). Both alternative back-splicing and alternative splicing inside circRNA are required for the biogenesis and diversity of circRNAs in animals Zhang et al, 2016;Feng et al, 2019;Zheng et al, 2019). In fact, alternative circularization of circRNA is reported as a common feature in rice, which results in a set of circRNA isoforms from the same locus Ye et al, 2017).…”

“…Complex splice sites can generate splice junctions with more than two donors or acceptors Zhang et al, 2016;Feng et al, 2019;Zheng et al, 2019). As alternative back-splicing events compete with the canonical splice site and alternative splice site, complex splice sites may have more chances to produce circRNAs.…”

Retracted: Circular RNA ciRS‐7 promotes tube formation in microvascular endothelial cells through downregulation of miR‐26a‐5p

“…Circular RNAs (circRNAs) are inventive races of RNAs belonging to noncoding RNA (ncRNA) that have been extensively explored in a variety of species by high‐throughput sequencing in recent years. [ 8 ] circRNAs have been broadly demonstrated to serve vital roles in heart diseases and mediate collective cellular mechanisms. [ 9 ] Furthermore, accumulating studies have explored that circRNAs participated in apoptosis, proliferation, migration, and inflammatory responses.…”

Circular RNA circ‐Ttc3 protects HaCaT cells from hypoxic injury by downregulation of miR‐449a

“…7 CircRNA mediates gene expression at the level of posttranscription or transcription by interacting with alternative molecules. 8 A growing number of research studies indicated that circRNA served an essential role in multiple biological progressions, including metastasis, migration, invasion and proliferation. 9 There were plenty of studies reported that circRNAs played vital roles in squamous cells carcinoma and gastric cancer.…”