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      Circular RNAs in human cancer

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          Abstract

          CircRNAs are a novel type of RNAs. With the newly developed technology of next-generation sequencing (NGS), especially RNA-seq technology, over 30,000 circRNAs have already been found. Owing to their unique structure, they are more stable than linear RNAs. CircRNAs play important roles in the carcinogenesis of cancer. The expression of circRNAs is correlated with patients’ clinical characteristics, and circRNAs play a vital role in many aspects of malignant phenotypes, including cell cycle, apoptosis, vascularization, and invasion; metastasis as a RNA sponge, binding to RBP; or translation. Therefore, it is meaningful to further study the mechanism of interactions between circRNAs and tumors. The role of circRNAs as molecular markers or potential targets will provide promising application perspectives, such as early tumor diagnosis, therapeutic evaluation, prognosis prediction, and even gene therapy for tumors.

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          CIRI: an efficient and unbiased algorithm for de novo circular RNA identification

          Yuan Gao, Jinfeng Wang, Fangqing Zhao (2015)
          Recent studies reveal that circular RNAs (circRNAs) are a novel class of abundant, stable and ubiquitous noncoding RNA molecules in animals. Comprehensive detection of circRNAs from high-throughput transcriptome data is an initial and crucial step to study their biogenesis and function. Here, we present a novel chiastic clipping signal-based algorithm, CIRI, to unbiasedly and accurately detect circRNAs from transcriptome data by employing multiple filtration strategies. By applying CIRI to ENCODE RNA-seq data, we for the first time identify and experimentally validate the prevalence of intronic/intergenic circRNAs as well as fragments specific to them in the human transcriptome. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0571-3) contains supplementary material, which is available to authorized users.
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            Diverse alternative back-splicing and alternative splicing landscape of circular RNAs

            Xiao-Ou Zhang, Rui Dong, Yang Zhang … (2016)
            Circular RNAs (circRNAs) derived from back-spliced exons have been widely identified as being co-expressed with their linear counterparts. A single gene locus can produce multiple circRNAs through alternative back-splice site selection and/or alternative splice site selection; however, a detailed map of alternative back-splicing/splicing in circRNAs is lacking. Here, with the upgraded CIRCexplorer2 pipeline, we systematically annotated different types of alternative back-splicing and alternative splicing events in circRNAs from various cell lines. Compared with their linear cognate RNAs, circRNAs exhibited distinct patterns of alternative back-splicing and alternative splicing. Alternative back-splice site selection was correlated with the competition of putative RNA pairs across introns that bracket alternative back-splice sites. In addition, all four basic types of alternative splicing that have been identified in the (linear) mRNA process were found within circRNAs, and many exons were predominantly spliced in circRNAs. Unexpectedly, thousands of previously unannotated exons were detected in circRNAs from the examined cell lines. Although these novel exons had similar splice site strength, they were much less conserved than known exons in sequences. Finally, both alternative back-splicing and circRNA-predominant alternative splicing were highly diverse among the examined cell lines. All of the identified alternative back-splicing and alternative splicing in circRNAs are available in the CIRCpedia database ( http://www.picb.ac.cn/rnomics/circpedia ). Collectively, the annotation of alternative back-splicing and alternative splicing in circRNAs provides a valuable resource for depicting the complexity of circRNA biogenesis and for studying the potential functions of circRNAs in different cells.
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              Oncogenic Role of Fusion-circRNAs Derived from Cancer-Associated Chromosomal Translocations.

              Jlenia Guarnerio, Marco Bezzi, Jong Jeong … (2016)
              Chromosomal translocations encode oncogenic fusion proteins that have been proven to be causally involved in tumorigenesis. Our understanding of whether such genomic alterations also affect non-coding RNAs is limited, and their impact on circular RNAs (circRNAs) has not been explored. Here, we show that well-established cancer-associated chromosomal translocations give rise to fusion circRNAs (f-circRNA) that are produced from transcribed exons of distinct genes affected by the translocations. F-circRNAs contribute to cellular transformation, promote cell viability and resistance upon therapy, and have tumor-promoting properties in in vivo models. Our work expands the current knowledge regarding molecular mechanisms involved in cancer onset and progression, with potential diagnostic and therapeutic implications.
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                Author and article information

                Contributors
                Zhaoyang Zeng: zengzhaoyang@csu.edu.cn
                Wei Xiong: xiongwei@csu.edu.cn
                Journal
                Journal ID (nlm-ta): Mol Cancer
                Journal ID (iso-abbrev): Mol. Cancer
                Title: Molecular Cancer
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1476-4598
                Publication date (Electronic): 31 January 2017
                Publication date PMC-release: 31 January 2017
                Publication date Collection: 2017
                Volume: 16
                Electronic Location Identifier: 25
                Affiliations
                [1 ]ISNI 0000 0001 0379 7164, GRID grid.216417.7, Key Laboratory of Carcinogenesis of Ministry of Health, Xiangya Hospital, , Central South University, ; Changsha, Hunan 410078 China
                [2 ]ISNI 0000 0001 0379 7164, GRID grid.216417.7, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, , Central South University, ; Changsha, Hunan 410078 China
                [3 ]ISNI 0000 0001 0379 7164, GRID grid.216417.7, Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, , Central South University, ; Changsha, Hunan 410013 China
                [4 ]ISNI 0000 0001 0379 7164, GRID grid.216417.7, Department of Stomatolog, The Second Xiangya Hospital, , Central South University, ; Changsha, Hunan 410011 China
                [5 ]ISNI 0000 0001 0379 7164, GRID grid.216417.7, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, , Central South University, ; Changsha, Hunan 410013 China
                [6 ]ISNI 0000 0001 0675 4725, GRID grid.239578.2, Department of Cancer Biology, , Lerner Research Institute, Cleveland Clinic, ; Cleveland, OH USA
                Article
                Publisher ID: 598
                DOI: 10.1186/s12943-017-0598-7
                PMC ID: 5282898
                PubMed ID: 28143578
                SO-VID: 6d52184d-e9f6-484c-8979-393a804392ad
                Copyright © © The Author(s). 2017
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 1 December 2016
                Date accepted : 19 January 2017
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81372907
                Award Recipient :
                Categories
                Subject: Review
                Custom metadata
                issue-copyright-statement © The Author(s) 2017

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: circular rnas,cancer,splicing,biomarker,regulation
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: circular rnas, cancer, splicing, biomarker, regulation

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