The DOI matches its Crossref record; 71 of the 71 references it cites were found in a registry or an index.
Circular RNA: A new star of noncoding RNAs
Abstract
Circular RNAs (circRNAs) are a novel type of RNA that, unlike linear RNAs, form a covalently closed continuous loop and are highly represented in the eukaryotic transcriptome. Recent studies have discovered thousands of endogenous circRNAs in mammalian cells. CircRNAs are largely generated from exonic or intronic sequences, and reverse complementary sequences or RNA-binding proteins (RBPs) are necessary for circRNA biogenesis. The majority of circRNAs are conserved across species, are stable and resistant to RNase R, and often exhibit tissue/developmental-stage-specific expression. Recent research has revealed that circRNAs can function as microRNA (miRNA) sponges, regulators of splicing and transcription, and modifiers of parental gene expression. Emerging evidence indicates that circRNAs might play important roles in atherosclerotic vascular disease risk, neurological disorders, prion diseases and cancer; exhibit aberrant expression in colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC); and serve as diagnostic or predictive biomarkers of some diseases. Similar to miRNAs and long noncoding RNAs (lncRNAs), circRNAs are becoming a new research hotspot in the field of RNA and could be widely involved in the processes of life. Herein, we review the formation and properties of circRNAs, their functions, and their potential significance in disease.
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“Originating from various genomic regions, circRNAs are synthesized by the back-splicing of protein-coding precursor mRNAs (primarily in eukaryotes) [25,26].”
From Circular RNAs in depression: Biogenesis, function, expression, and therapeutic potential (2021) · cites this paper as [25]
Citations
Cites
Circular RNAs are a large class of animal RNAs with regulatory potency
Memczak, S., Jens, M., Elefsinioti, A., Torti, F., Krueger, J., Rybak, A., Maier, L., Mackowiak, S. D., Gregersen, L. H., Munschauer, M., et al. (2013) · Nature · doi:10.1038/nature11928 · Cited by 7,990
Natural RNA circles function as efficient microRNA sponges
Hansen, T. B., Jensen, T. I., Clausen, B. H., Bramsen, J. B., Finsen, B., Damgaard, C. K., & Kjems, J. (2013) · Nature · doi:10.1038/nature11993 · Cited by 7,985
Oncomirs—MicroRNAs with a role in cancer
Esquela-Kerscher, A., & Slack, F. J. (2006) · Nature Reviews Cancer · doi:10.1038/nrc1840 · Cited by 5,884
Circular RNAs are abundant, conserved, and associated with ALU repeats
Jeck, W. R., Sorrentino, J. A., Wang, K., Slevin, M. K., Burd, C. E., Liu, J., Marzluff, W. F., & Sharpless, N. E. (2013) · RNA · doi:10.1261/rna.035667.112 · Cited by 4,388
circRNA biogenesis competes with pre-mRNA splicing
Ashwal-Fluss, R., Meyer, M., Pamudurti, N. R., Ivanov, A., Bartok, O., Hanan, M., Evantal, N., Memczak, S., Rajewsky, N., & Kadener, S. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.08.019 · Cited by 3,083
Exon-intron circular RNAs regulate transcription in the nucleus
Li, Z., Huang, C., Bao, C., Chen, L., Lin, M., Wang, X., Zhong, G., Yu, B., Hu, W., Dai, L., et al. (2015) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2959 · Cited by 2,905
Detecting and characterizing circular RNAs
Jeck, W. R., & Sharpless, N. E. (2014) · Nature Biotechnology · doi:10.1038/nbt.2890 · Cited by 2,710
Sanger, H. L., Klotz, G., Riesner, D., Gross, H. J., & Kleinschmidt, A. K. (1976) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.73.11.3852 · Cited by 2,296
Salzman, J., Gawad, C., Wang, P. L., Lacayo, N., & Brown, P. O. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030733 · Cited by 2,239
Circular intronic long noncoding RNAs
Zhang, Y., Zhang, X.-O., Chen, T., Xiang, J.-F., Yin, Q.-F., Xing, Y.-H., Zhu, S., Yang, L., & Chen, L.-L. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.08.017 · Cited by 2,221
The RNA Binding Protein Quaking Regulates Formation of circRNAs
Conn, S. J., Pillman, K. A., Toubia, J., Conn, V. M., Salmanidis, M., Phillips, C. A., Roslan, S., SCHREIBER, A. W., Gregory, P. A., & Goodall, G. J. (2015) · Cell · doi:10.1016/j.cell.2015.02.014 · Cited by 2,205
Complementary Sequence-Mediated Exon Circularization
Zhang, X.-O., Wang, H.-B., Zhang, Y., Lu, X., Chen, L.-L., & Yang, L. (2014) · Cell · doi:10.1016/j.cell.2014.09.001 · Cited by 1,999 · cited 3×
“first proposed a model of alternative circularization that is similar to alternative splicing [18] (Fig.”
BackgroundInfluentialRegulation of circRNA biogenesis
Chen, L.-L., & Yang, L. (2015) · RNA Biology · doi:10.1080/15476286.2015.1020271 · Cited by 1,953
Cell-Type Specific Features of Circular RNA Expression
Salzman, J., Chen, R. E., Olsen, M. N., Wang, P., & Brown, P. O. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003777 · Cited by 1,952
circBase: a database for circular RNAs
Glažar, P., Papavasileiou, P., & Rajewsky, N. (2014) · RNA · doi:10.1261/rna.043687.113 · Cited by 1,908
Garzon, R., Calin, G. A., & Croce, C. M. (2009) · Annual Review of Medicine · doi:10.1146/annurev.med.59.053006.104707 · Cited by 1,816
Expanded identification and characterization of mammalian circular RNAs
Guo, J. U., Agarwal, V., Guo, H., & Bartel, D. P. (2014) · Genome biology · doi:10.1186/s13059-014-0409-z · Cited by 1,591
Circular RNAs: diversity of form and function
Lasda, E. L., & Parker, R. (2014) · RNA · doi:10.1261/rna.047126.114 · Cited by 1,201
Mis-splicing yields circular RNA molecules.
Cocquerelle, C., Mascrez, B., Hétuin, D., & Bailleul, B. (1993) · The FASEB Journal · doi:10.1096/fasebj.7.1.7678559 · Cited by 1,197
Long non-coding RNAs: A new frontier in the study of human diseases
Shi, X., Sun, M., Liu, H., Yao, Y., & Song, Y. (2013) · Cancer Letters · doi:10.1016/j.canlet.2013.06.013 · Cited by 1,156
Circular transcripts of the testis-determining gene Sry in adult mouse testis
Capel, B., Swain, A., Nicolis, S. K., Hacker, A., Walter, M. A., Koopman, P. A., Goodfellow, P. N., & Lovell-Badge, R. H. (1993) · Cell · doi:10.1016/0092-8674(93)90279-y · Cited by 1,112
Analysis of Intron Sequences Reveals Hallmarks of Circular RNA Biogenesis in Animals
Ivanov, A., Memczak, S., Wyler, E., Torti, F., Porath, H. T., Orejuela, M. R., Piechotta, M., Levanon, E. Y., Landthaler, M., Dieterich, C., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.12.019 · Cited by 1,107
Electron microscopic evidence for the circular form of RNA in the cytoplasm of eukaryotic cells
HSU, M.-T., & COCA-PRADOS, M. (1979) · Nature · doi:10.1038/280339a0 · Cited by 1,021
miRNA‐dependent gene silencing involving Ago2‐mediated cleavage of a circular antisense RNA
Hansen, T. B., Wiklund, E. D., Bramsen, J. B., Villadsen, S. B., Statham, A. L., Clark, S. J., & Kjems, J. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.359 · Cited by 996
Westholm, J. O., Miura, P., Olson, S., Shenker, S., Joseph, B. J., Sanfilippo, P., Celniker, S., Graveley, B. R., & Lai, E. C. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.10.062 · Cited by 990
Short intronic repeat sequences facilitate circular RNA productionPreprint
Liang, D., & Wilusz, J. E. (2014) · Genes & Development · doi:10.1101/gad.251926.114 · Cited by 964
Circular RNA and miR-7 in Cancer
Hansen, T. B., Kjems, J., & Damgaard, C. K. (2013) · Cancer Research · doi:10.1158/0008-5472.can-13-1568 · Cited by 920
Burd, C. E., Jeck, W. R., Liu, Y., Sanoff, H. K., Wang, Z., & Sharpless, N. E. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1001233 · Cited by 909
Nigro, J. M., Cho, K. R., Fearon, E. R., Kern, S. E., Ruppert, J. M., Oliner, J., Kinzler, K. W., & Vogelstein, B. (1991) · Cell · doi:10.1016/0092-8674(91)90244-s · Cited by 906
Using circular RNA as a novel type of biomarker in the screening of gastric cancer
Li, P., Chen, S., Chen, H., Mo, X., Li, T., Shao, Y., Xiao, B., & Guo, J. (2015) · Clinica Chimica Acta · doi:10.1016/j.cca.2015.02.018 · Cited by 777
Exon Circularization Requires Canonical Splice Signals
Starke, S., Jost, I., Roßbach, O., Schneider, T. P., Schreiner, S., Hung, L.-H., & Bindereif, A. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.12.002 · Cited by 774
Initiation of Protein Synthesis by the Eukaryotic Translational Apparatus on Circular RNAs
Chen, C.-Y., & Sarnow, P. (1995) · Science · doi:10.1126/science.7536344 · Cited by 766
Circular RNA Is Expressed across the Eukaryotic Tree of Life
Wang, P., Bao, Y., Yee, M., Barrett, S. P., Hogan, G. J., Olsen, M. N., Dinneny, J. R., Brown, P. O., & Salzman, J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0090859 · Cited by 751
Bachmayr-Heyda, A., Reiner, A. T., Auer, K., Sukhbaatar, N., Aust, S., Bachleitner‐Hofmann, T., Mesteri, I., Grunt, T. W., Zeillinger, R., & Pils, D. (2015) · Scientific Reports · doi:10.1038/srep08057 · Cited by 736
Efficient backsplicing produces translatable circular mRNAs
Wang, Y., & Wang, Z. (2014) · RNA · doi:10.1261/rna.048272.114 · Cited by 676
The Landscape of MicroRNA, Piwi-Interacting RNA, and Circular RNA in Human Saliva
Bahn, J. H., Zhang, Q., Li, F., Chan, T.-M., Lin, X., Kim, Y. D., Wong, D. T., & Xiao, X. G. (2014) · Clinical Chemistry · doi:10.1373/clinchem.2014.230433 · Cited by 653
The hepatitis delta (δ) virus possesses a circular RNA
Kos, A., Dijkema, R., Arnberg, A. C., van der Meide, P. H., & Schellekens, H. (1986) · Nature · doi:10.1038/323558a0 · Cited by 651
Kefas, B., Godlewski, J., Comeau, L., Li, Y., Abounader, R., Hawkinson, M., Lee, J., Fine, H., Chiocca, E. A., Lawler, S., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-6639 · Cited by 647
Circular RNA (circRNA) in Alzheimer’s disease (AD)
Lukiw, W. J. (2013) · Frontiers in Genetics · doi:10.3389/fgene.2013.00307 · Cited by 636
Circular RNA ITCH has inhibitory effect on ESCC by suppressing the Wnt/β-catenin pathway
Li, F., Zhang, L., Li, W., Deng, J., Zheng, J., An, M., Lü, J., & Zhou, Y. (2015) · Oncotarget · doi:10.18632/oncotarget.3469 · Cited by 634
Repression of α-synuclein expression and toxicity by microRNA-7
Junn, E., Lee, K.-W., Jeong, B. S., Chan, T. W., Im, J.-Y., & Mouradian, M. M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0906277106 · Cited by 634
Transcriptome-wide discovery of circular RNAs in Archaea
Danan, M., Schwartz, S., Edelheit, S., & Sorek, R. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr1009 · Cited by 560
A Circuitous Route to Noncoding RNA
Wilusz, J. E., & Sharp, P. A. (2013) · Science · doi:10.1126/science.1238522 · Cited by 531
Circular RNAs: splicing’s enigma variations
Hentze, M. W., & Preiss, T. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.53 · Cited by 455
Ghosal, S., Das, S., Sen, R., Basak, P., & Chakrabarti, J. (2013) · Frontiers in Genetics · doi:10.3389/fgene.2013.00283 · Cited by 444
A View of Pre-mRNA Splicing from RNase R Resistant RNAs
Suzuki, H., & Tsukahara, T. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms15069331 · Cited by 432
RNA circularization strategies in vivo and in vitro
Petkovic, S., & Müller, S. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv045 · Cited by 386
Vicens, Q., & Westhof, É. (2014) · Cell · doi:10.1016/j.cell.2014.09.005 · Cited by 373
Exon Skipping Is Correlated with Exon Circularization
Kelly, S. L., Greenman, C., Cook, P. R., & Papantonis, A. (2015) · Journal of Molecular Biology · doi:10.1016/j.jmb.2015.02.018 · Cited by 372
Humphries, B. A., & Yang, C. (2015) · Oncotarget · doi:10.18632/oncotarget.3052 · Cited by 343
Circular RNAs from transcripts of the rat cytochrome P450 2C24 gene: correlation with exon skipping.
Zaphiropoulos, P. G. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.13.6536 · Cited by 246
Some yeast mitochondrial RNAs are circular
Arnberg, A. C., van Ommen, G. B., Grivell, L. A., Bruggen, E. F. J. V., & Borst, P. (1980) · Cell · doi:10.1016/0092-8674(80)90505-x · Cited by 234
Jiang, L., Liu, X., Chen, Z., Jin, Y., Heidbreder, C. E., Kolokythas, A., Wang, A., Dai, Y. D., & Zhou, X. C. (2010) · Biochemical Journal · doi:10.1042/bj20100859 · Cited by 205
Long noncoding RNAs: Novel insights into gastric cancer
Fang, X., Pan, H., Leng, R., & Ye, D. (2014) · Cancer Letters · doi:10.1016/j.canlet.2014.11.005 · Cited by 198
Exon circularization in mammalian nuclear extracts.
Pasman, Z., Been, M. D., & García-Blanco, M. A. (1996) · PubMed · Cited by 185
Circular RNAs are depleted of polymorphisms at microRNA binding sites
Thomas, L. F., & Sætrom, P. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu257 · Cited by 178
Dropcho, E. J., Chen, Y. T., Posner, J. B., & Old, L. J. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.13.4552 · Cited by 162
The Mouse formin (Fmn) Gene: Abundant Circular RNA Transcripts and Gene-Targeted Deletion Analysis
Chao, C. W., Chan, D. C., Kuo, A., & Leder, P. (1998) · Molecular Medicine · doi:10.1007/bf03401761 · Cited by 158
Inverted repeats are necessary for circularization of the mouse testis Sry transcript
Dubin, R. A., Kazmi, M. A., & D, H. O. M. (1995) · Gene · doi:10.1016/0378-1119(95)00639-7 · Cited by 154
Circular mRNA can direct translation of extremely long repeating-sequence proteins in vivo
Perriman, R., & Ares, M. (1998) · RNA · doi:10.1017/s135583829898061x · Cited by 152
From pseudo-ceRNAs to circ-ceRNAs: a tale of cross-talk and competition
Taulli, R., Loretelli, C., & Pandolfi, P. P. (2013) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2580 · Cited by 132
Life without A tail: New formats of long noncoding RNAs
Zhang, Y., Yang, L. C., & Chen, L. (2013) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2013.10.009 · Cited by 132
microRNA-7: A tumor suppressor miRNA with therapeutic potential
Kalinowski, F. C., Brown, R. A. M., Ganda, C., Giles, K. M., Epis, M. R., Horsham, J. L., & Leedman, P. J. (2014) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2014.05.040 · Cited by 129
Suto, T., Yokobori, T., Yajima, R., Morita, H., Fujii, T., Yamaguchi, S., Altan, B., Tsutsumi, S., Asao, T., & Kuwano, H. (2014) · Carcinogenesis · doi:10.1093/carcin/bgu242 · Cited by 127
Introns excised from the Delta primary transcript are localized near sites of Delta transcription.
Kopczynski, C., & Muskavitch, M. A. T. (1992) · The Journal of Cell Biology · doi:10.1083/jcb.119.3.503 · Cited by 79
A spliced intron accumulates as a lariat in the nucleus of T cells
Qian, L., Vu, M. N., Carter, M., & Wilkinson, M. F. (1992) · Nucleic Acids Research · doi:10.1093/nar/20.20.5345 · Cited by 78
Life cycle and pathogenesis of hepatitis D virus: A review
Abbas, Z. (2013) · World Journal of Hepatology · doi:10.4254/wjh.v5.i12.666 · Cited by 77
MiR-7 Promotes Epithelial Cell Transformation by Targeting the Tumor Suppressor KLF4
Meza‐Sosa, K. F., Pérez-García, E. I., Camacho‐Concha, N., López-Gutiérrez, O., Pedraza‐Alva, G., & Pérez‐Martínez, L. (2014) · PLoS ONE · doi:10.1371/journal.pone.0103987 · Cited by 60
Gene Expression Profile Following Stable Expression of the Cellular Prion Protein
Satoh, J., & Yamamura, T. (2004) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-004-6920-0 · Cited by 48
Hao, Z., Yang, J., Wang, C., Li, Y., Zhang, Y., Dong, X., Zhou, L., Liu, J., Zhang, Y., & Qian, J. (2015) · Europe PMC (PubMed Central) · Cited by 47
Hepatitis Delta Virus: A Peculiar Virus
Alves, C., Branco, C., & Cunha, C. V. (2013) · Advances in Virology · doi:10.1155/2013/560105 · Cited by 38
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ceRNA in cancer: possible functions and clinical implications
Qi, X., Zhang, D., Wu, N., Xiao, J., Wang, X., & Ma, W. (2015) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2015-103334 · Cited by 1,273
Zhang, X., Wang, S., Wang, H., Cao, J., Huang, X., Chen, Z., Xu, P., Sun, G., Xu, J., Lv, J., et al. (2019) · Molecular Cancer · doi:10.1186/s12943-018-0935-5 · Cited by 832
RetractedCircRNA: a novel type of biomarker for cancer
Zhang, H.-D., Jiang, L., Sun, D., Hou, J., & Ji, Z. (2017) · Breast Cancer · doi:10.1007/s12282-017-0793-9 · Cited by 764
“In addition, circRNAs are produced mainly by exons and introns sequences, but the reverse complementary sequences or RNA-binding proteins (RBPs) are essential for circRNA formation [14].”
BackgroundCircular RNAs are miRNA sponges and can be used as a new class of biomarker
Kulcheski, F. R., Christoff, A. P., & Margis, R. (2016) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2016.09.011 · Cited by 741
Oncogenic Role of Fusion-circRNAs Derived from Cancer-Associated Chromosomal Translocations
Guarnerio, J., Bezzi, M., Jeong, J. C., Paffenholz, S. V., Berry, K., Naldini, M. M., Lo‐Coco, F., Tay, Y., Beck, A. H., & Pandolfi, P. P. (2016) · Cell · doi:10.1016/j.cell.2016.03.020 · Cited by 740
Metadata
- Authors
- Qu, S., Yang, X., Li, X., Wang, J., Gao, Y., Shang, R., Sun, W., Dou, K., & Li, H.
- Affiliations
- Xijing Hospital (CN)
- Corresponding author
- Li, Haimin
- Venue
- Cancer Letters
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 365
- Issue
- 2
- Pages
- 141-148
- ISSN
- 0304-3835 (ISSN-L)
- OpenAlex
- W1866220599
- Cited by
- 1,808
- References
- 71
- Citations by year
- 2026: 30 · 2025: 71 · 2024: 142 · 2023: 176 · 2022: 236 · 2021: 328 · 2020: 326 · 2019: 205 · 2018: 154 · 2017: 75 · 2016: 52 · 2015: 7
- FWCI
- 9.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81772061)
- Health Public Welfare Industry Special Scientific Research Projects of China (201202007)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Circular RNAs in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- circular RNA, circRNA biogenesis, RNA-binding proteins, microRNA sponge, RNA splicing regulation, transcriptional regulation, circRNA stability, disease biomarkers, colorectal cancer, pancreatic ductal adenocarcinoma, atherosclerosis, neurological disorders, prion disease, long non-coding RNA
- MeSH terms
- RNA, Circular, Exoribonucleases, Gene Expression Regulation, Humans, Neoplasms, RNA, RNA Splicing, Transcription, Genetic, RNA, Untranslated
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