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Circular RNAs: Biogenesis, Function, and a Role as Possible Cancer Biomarkers
Open accessAbstract
Circular RNAs (circRNAs) are a class of noncoding RNAs (ncRNAs) that form covalently closed continuous loop structures, lacking the terminal 5 ′ and 3 ′ ends. CircRNAs are generated in the process of back-splicing and can originate from different genomic regions. Their unique circular structure makes circRNAs more stable than linear RNAs. In addition, they also display insensitivity to ribonuclease activity. Generally, circRNAs function as microRNA (miRNA) sponges and have a regulatory role in transcription and translation. They may be also translated in a cap-independent manner in vivo, to generate specific proteins. In the last decade, next-generation sequencing techniques, especially RNA-seq, have revealed great abundance and also dysregulation of many circRNAs in various diseases, suggesting their involvement in disease development and progression. Regarding their high stability and relatively specific differential expression patterns in tissues and extracellular environment (e.g., body fluids), they are regarded as promising novel biomarkers in cancer. Therefore, we focus this review on describing circRNA biogenesis, function, and involvement in human cancer development and address the potential of circRNAs to be effectively used as novel cancer diagnostic and prognostic biomarkers.
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![Figure 1 Schematic representation of circRNA biogenesis. (a) Canonical pre-mRNA splicing, yielding a mature mRNA molecule. (b) Lariat-driven circularization (exon skipping). Following canonical splicing, exons in exon-containing lariats undergo back-splicing and circularization, which results in the formation of ecircRNA or EIciRNA molecules. (c) Intron pairing-driven circularization, utilizing coupling of flanking introns by direct base pairing between cis-acting regulatory elements that contain reverse complementary sequences (e.g., Alu repeats). Intron pairing is followed by back-splicing and exon circularization. (d) CircRNA biogenesis, mediated by trans-acting factors, such as RNA-binding proteins (RBPs) (e.g., QKI, MBL/MBNL1) that bind to specific sequence motifs of flanking introns on linear pre-mRNA, dimerize, and facilitate back-splicing and exon circularization. (e) Regulation of circRNA biogenesis by the RNA-editing enzyme ADAR. ADAR destabilizes intron base pairing interactions through the action of adenosine-to-inosine (A-to-I) editing, which impairs pre-mRNA looping and diminishes exon circularization. (f) Resplicing-driven circularization. EcircRNAs may be formed from mature mRNA exons that undergo back-splicing and circularization. (g) Formation of ciRNAs from intron lariats that escape the usual intron debranching and degradation, following the canonical pre-mRNA splicing. (h) Formation of intergenic circRNAs. This figure is adapted from Wang et al. [151].](/paper-figures/f737a9939afe4c49bf92060003f458d7/circular-rnas-biogenesis-function-and-a-role-as-possible-cancer-biomarkers-figure-1.jpg)
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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 [26]
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6 retracted
circRNA_100290 plays a role in oral cancer by functioning as a sponge of the miR-29 family
Chen, L., Zhang, S., Wu, J., Cui, J., Zhong, L., Zeng, L., & Ge, S. (2017) · Oncogene · doi:10.1038/onc.2017.89 · Cited by 391
RetractedYu, L., Gong, X., Sun, L., Zhou, Q., Lu, B., & Zhū, L. (2016) · PLoS ONE · doi:10.1371/journal.pone.0158347 · Cited by 359 · cited 3×
“In addition, knockdown of ciRS-7 in HCC cell lines suppressed cell invasion and proliferation through miR-7 targeting [91].”
BackgroundInfluentialRetractedRETRACTED ARTICLE: Circular RNA 0000096 affects cell growth and migration in gastric cancer
Li, P., Chen, H., Chen, S., Mo, X., Li, T., Xiao, B., Yu, R., & Guo, J. (2017) · British Journal of Cancer · doi:10.1038/bjc.2016.451 · Cited by 228
RetractedTumor suppressor role of miR-217 in human epithelial ovarian cancer by targeting IGF1R
Li, J., Li, D., & Zhang, W. (2015) · Oncology Reports · doi:10.3892/or.2015.4498 · Cited by 43
RetractedThe MicroRNA-217 Functions as a Potential Tumor Suppressor in Gastric Cancer by Targeting GPC5
Wang, H., Dong, X., Gu, X., Qin, R., Jia, H., & Gao, J. (2015) · PLoS ONE · doi:10.1371/journal.pone.0125474 · Cited by 40
RetractedCircular RNA hsa_circ_0001564 facilitates tumorigenesis of osteosarcoma via sponging miR-29c-3p
Li, J., & Song, Y.-Z. (2017) · Tumor Biology · doi:10.1177/1010428317709989 · Cited by 10 · cited 1×
“Hsa_circ_0001564 CANX Osteosarcoma Up NA Sponge: miR-29c-3p [114]”
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MicroRNAs: Target Recognition and Regulatory Functions
Bartel, D. P. (2009) · Cell · doi:10.1016/j.cell.2009.01.002 · Cited by 20,068 · cited 1×
“miRNAs are approximately 22nt long ncRNAs, involved in posttranscriptional regulation of gene expression, which act by direct binding to specific target sites within UTRs of mRNAs [40, 41].”
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 · cited 9×
“However, they may be also formed from intronic, noncoding, antisense, 3′ UTR, 5′ UTR, or intergenic genomic regions [9, 17].”
BackgroundInfluentialNatural 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
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BackgroundLong non-coding RNAs: insights into functions
Mercer, T. R., Dinger, M. E., & Mattick, J. S. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2521 · Cited by 5,654 · cited 1×
“Thus, these findings strongly imply that circRNAs could function as scaffolds for RBPs regulating transcription, as it had been determined for several lncRNAs [52, 53].”
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“0 distinctive features facilitate annotation, graphic visualization, analysis, and discovery of miRNA-mRNA, miRNA-circRNA, miRNA-pseudogene, miRNA-lncRNA, and protein-RNA interaction networks and RBP binding sites [60].”
BackgroundCircular 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 · cited 6×
“In addition, circRNAs appear to be stably expressed in a cell/tissue-dependent and developmental stage-specific manner [3, 9, 11, 12].”
BackgroundInfluentialGenome Regulation by Long Noncoding RNAs
Rinn, J. L., & Chang, H. Y. (2012) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-051410-092902 · Cited by 4,091 · cited 1×
“Thus, these findings strongly imply that circRNAs could function as scaffolds for RBPs regulating transcription, as it had been determined for several lncRNAs [52, 53].”
BackgroundcircRNA 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 · cited 3×
“It has been demonstrated that circRNAs can bind to several RBPs (Figure 2(b)), including AGO [9, 34], RNA polymerase II [17], QKI [27], EIF4A3 [51], and MBL [28].”
BackgroundExon-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 · cited 9×
“CircRNAs form a large group of transcriptional and posttranscriptional regulators, and their direct involvement in regulating gene expression has been demonstrated in several studies [9, 17, 21].”
BackgroundInfluentialDetecting and characterizing circular RNAs
Jeck, W. R., & Sharpless, N. E. (2014) · Nature Biotechnology · doi:10.1038/nbt.2890 · Cited by 2,710 · cited 6×
“In the pseudo-referencebased [73] or candidate-based approach [22], all possible combinations of candidate circRNAs are constructed.”
BackgroundInfluentialCircular RNAs in the Mammalian Brain Are Highly Abundant, Conserved, and Dynamically Expressed
Rybak-Wolf, A., Stottmeister, C., Glažar, P., Jens, M., Pino, N., Giusti, S., Hanan, M., Behm, M., Bartok, O., Ashwal-Fluss, R., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.03.027 · Cited by 2,423 · cited 2×
“High ADAR expression destabilizes intron base pairing interactions, impairing pre-mRNA looping and decreasing the likelihood of pre-mRNA circularization and circRNA formation, for a subset of circRNAs [25, 29].”
BackgroundSalzman, J., Gawad, C., Wang, P. L., Lacayo, N., & Brown, P. O. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030733 · Cited by 2,239 · cited 4×
“EcircRNAs are the most abundant circRNA type, accounting for over 80% of identified circRNAs, and are predominantly located in the cytoplasm [3, 9, 12], though the exact process of nuclear export remains to be elucidated.”
BackgroundInfluentialCircular 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
Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis
Li, Y., Zheng, Q., Bao, C., Li, S., Guo, W., Zhao, J., Chen, D., Gu, J., He, X., & Huang, S. (2015) · Cell Research · doi:10.1038/cr.2015.82 · Cited by 2,210
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 · cited 2×
“It has been demonstrated that circRNAs can bind to several RBPs (Figure 2(b)), including AGO [9, 34], RNA polymerase II [17], QKI [27], EIF4A3 [51], and MBL [28].”
BackgroundCirc-ZNF609 is a circular RNA that can be translated and functions in myogenesis
Legnini, I., Di Timoteo, G., Rossi, F., Morlando, M., Briganti, F., Sthandier, O., Fatica, A., Santini, T., Andronache, A., Wade, M., et al. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.02.017 · Cited by 2,173 · cited 1×
“However, molecular activity of circZNF609-derived proteins still needs to be determined [38].”
BackgroundMicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells
Ebert, M. S., Neilson, J. R., & Sharp, P. A. (2007) · Nature Methods · doi:10.1038/nmeth1079 · Cited by 2,108 · cited 1×
“Overall, when compared to linear miRNA sponges, circRNAs have proven themselves as more stable and therefore more effective [48, 49].”
BackgroundZheng, Q., Bao, C., Guo, W., Li, S., Chen, J., Chen, B., Luo, Y., Lyu, D., Li, Y., Shi, G., et al. (2016) · Nature Communications · doi:10.1038/ncomms11215 · Cited by 2,041 · cited 1×
“CircHIPK3 HIPK3 HCC Up NA Sponge: miR-124 [101]”
CPAT: Coding-Potential Assessment Tool using an alignment-free logistic regression model
Wang, L., Park, H. J., Dasari, S., Wang, S., Kocher, J., & Li, W. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt006 · Cited by 2,003 · cited 2×
“In addition, several integrated tools aimed to identify circRNAs with a protein-coding potential have been developed, including CircPro [74], IRESite [75], CPAT [76], Pfam 31.0 [77], PhyloCSF [78], and ORF Finder from the NCBI database.”
MethodInfluentialComplementary 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 4×
“, Alu elements) that may promote intron pairing, and exon circularization [12, 24, 25].”
BackgroundMethodInfluentialCell-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 · cited 3×
“In addition, circRNAs appear to be stably expressed in a cell/tissue-dependent and developmental stage-specific manner [3, 9, 11, 12].”
BackgroundcircBase: a database for circular RNAs
Glažar, P., Papavasileiou, P., & Rajewsky, N. (2014) · RNA · doi:10.1261/rna.043687.113 · Cited by 1,911 · cited 2×
“org/ A collection of merged and unified datasets of circRNAs, with evidence supporting their expression [57]”
BackgroundExtensive translation of circular RNAs driven by N6-methyladenosine
Yang, Y., Fan, X., Mao, M., Song, X., Wu, P., Zhang, Y., Jin, Y., Yang, Y., Chen, L.-L., Wang, Y., et al. (2017) · Cell Research · doi:10.1038/cr.2017.31 · Cited by 1,855 · cited 1×
“The study revealed that m(6)A motifs are enriched in many circRNAs and enable protein translation in a cap-independent manner, involving the m(6)A reader YTHDF3 and translation initiation factors eIF4G2 and eIF3A [39].”
BackgroundPamudurti, N. R., Bartok, O., Jens, M., Ashwal-Fluss, R., Stottmeister, C., Ruhe, L., Hanan, M., Wyler, E., Perez-Hernandez, D., Ramberger, E., et al. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.02.021 · Cited by 1,810
Foxo3 circular RNA retards cell cycle progression via forming ternary complexes with p21 and CDK2
Du, W. W., Yang, W., Liu, E., Yang, Z., Dhaliwal, P., & Yang, B. B. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw027 · Cited by 1,699 · cited 1×
“The circ-Foxo3-p21-CDK2 ternary complex can suppress cell cycle progression and inhibit tumor growth [96].”
BackgroundExpanded 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 · cited 2×
“Furthermore, cir-ZNF609 [45], mm9_circ_012559 [46], and circRNAs from the human C2H2 zinc finger gene family [47] have also been assumed to function as miRNA sponges.”
BackgroundCircInteractome: A web tool for exploring circular RNAs and their interacting proteins and microRNAs
Dudekula, D. B., Panda, A. C., Grammatikakis, I., De, S., Abdelmohsen, K., & Gorospe, M. (2015) · RNA Biology · doi:10.1080/15476286.2015.1128065 · Cited by 1,252 · cited 7×
“CircInteractome also enables the identification of potential circRNAs that act as RBP sponges, designing junction-spanning primers for specific circRNA detection, designing siRNAs for circRNA silencing, and identifying potential IRES [51].”
BackgroundMethodInfluentialThe Landscape of long noncoding RNA classification
Laurent, G. S., Wahlestedt, C., & Kapranov, P. (2015) · Trends in Genetics · doi:10.1016/j.tig.2015.03.007 · Cited by 1,211 · cited 2×
“The small ncRNAs include microRNAs (miRNAs), small nuclear RNAs (snRNAs), PIWI-interacting RNAs (piRNAs), small interfering RNAs (siRNAs), small nucleolar RNAs (snoRNAs), and others [1], whereas lncRNAs comprise long intergenic ncRNAs (lincRNAs), intronic ncRNAs, macroRNAs, sense ncRNA, antisense RNAs, and others [2].”
Circular RNAs: diversity of form and function
Lasda, E. L., & Parker, R. (2014) · RNA · doi:10.1261/rna.047126.114 · Cited by 1,201 · cited 1×
“However, some exonic and intronic circRNAs were shown to be shorter than 200 or even 100nt [5].”
BackgroundMapSplice: Accurate mapping of RNA-seq reads for splice junction discovery
Wang, K., Singh, D., Zeng, Z., Coleman, S. J., Huang, Y., Savich, G. L., He, X., Mieczkowski, P., Grimm, S. A., Perou, C. M., et al. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq622 · Cited by 1,193 · cited 2×
“Among the described circRNA detection tools, which were also compared with regard to their precision and sensitivity, were circRNA_ finder [64], CIRCexplorer [24], DCC [65], find_circ [9], UROBORUS [66], PTESFinder [67], KNIFE [68], CIRI [69], MapSplice [70], segemehl [71], and NCLscan [72].”
MethodNeural circular RNAs are derived from synaptic genes and regulated by development and plasticity
You, X., Vlatkovic, I., Babic, A., Will, T., Epstein, I., Tushev, G., Akbalik, G., Wang, M., Glock, C., Quedenau, C., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.3975 · Cited by 1,149 · cited 1×
“On the other hand, several studies implied that most circRNAs do not act like miRNA sponges, since the majority does not have more miRNA binding sites than colinear mRNAs [47, 50].”
BackgroundCIRI: an efficient and unbiased algorithm for de novo circular RNA identification
Gao, Y., Wang, J., & Zhao, F. (2015) · Genome biology · doi:10.1186/s13059-014-0571-3 · Cited by 1,115 · cited 2×
“Among the described circRNA detection tools, which were also compared with regard to their precision and sensitivity, were circRNA_ finder [64], CIRCexplorer [24], DCC [65], find_circ [9], UROBORUS [66], PTESFinder [67], KNIFE [68], CIRI [69], MapSplice [70], segemehl [71], and NCLscan [72].”
MethodCircular 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 · cited 2×
“Mouse testis-specific sex-determining region Y (Sry) linear isoform is expressed in the developing genital ridge and has a fundamental role as a transcription factor in sex determination [43].”
BackgroundAnalysis 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 · cited 3×
“High ADAR expression destabilizes intron base pairing interactions, impairing pre-mRNA looping and decreasing the likelihood of pre-mRNA circularization and circRNA formation, for a subset of circRNAs [25, 29].”
BackgroundNon‐coding RNAs: regulators of disease
Taft, R. J., Pang, K. C., Mercer, T. R., Dinger, M. E., & Mattick, J. S. (2009) · The Journal of Pathology · doi:10.1002/path.2638 · Cited by 1,080 · cited 2×
“Generally, miRNAs are included in various cell processes, including cellular differentiation, development, proliferation, and apoptosis, where they play an important role as regulators of gene expression [81].”
BackgroundHsu, S., Tseng, Y., Shrestha, S., Lin, Y., Khaleel, A., Chou, C., Chu, C.-F., Huang, H., Lin, C.-M., Ho, S.-Y., et al. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt1266 · Cited by 1,044
Diverse alternative back-splicing and alternative splicing landscape of circular RNAsPreprint
Zhang, X.-O., Dong, R., Zhang, Y., Zhang, J., Luo, Z. D., Zhang, J., Chen, L., & Yang, L. C. (2016) · Genome Research · doi:10.1101/gr.202895.115 · Cited by 1,036 · cited 3×
“cn/rnomics/circpedia/ A database holding information on identified and annotated back-splicing and alternative splicing in circRNAs from human, mouse, fly, and worm samples [19]”
BackgroundInfluentialPhyloCSF: a comparative genomics method to distinguish protein coding and non-coding regionsPreprint
Lin, M. F., Jungreis, I., & Kellis, M. (2010) · Nature Precedings · doi:10.1093/bioinformatics/btr209 · Cited by 1,031 · cited 2×
“In addition, several integrated tools aimed to identify circRNAs with a protein-coding potential have been developed, including CircPro [74], IRESite [75], CPAT [76], Pfam 31.0 [77], PhyloCSF [78], and ORF Finder from the NCBI database.”
BackgroundInfluentialmiRNA‐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 · cited 1×
“The combination of ciRS-7 and miR-671 triggers the linearization and AGO2-mediated cleavage of ciRS-7, which enables the release of the absorbed miR-7 molecules [42].”
BackgroundWestholm, 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 · cited 1×
“Among the described circRNA detection tools, which were also compared with regard to their precision and sensitivity, were circRNA_ finder [64], CIRCexplorer [24], DCC [65], find_circ [9], UROBORUS [66], PTESFinder [67], KNIFE [68], CIRI [69], MapSplice [70], segemehl [71], and NCLscan [72].”
MethodShort intronic repeat sequences facilitate circular RNA productionPreprint
Liang, D., & Wilusz, J. E. (2014) · Genes & Development · doi:10.1101/gad.251926.114 · Cited by 964 · cited 2×
“In some cases, increased stability of intron base pairing prevented circRNA formation [26].”
BackgroundCircular 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 921 · cited 5×
“Since circRNA ciRS-7 acts as a miR-7 sponge, quenching the activity of miR-7 may increase the expression levels of miR-7 target oncogenes, resulting in a decreased tumor suppression [83].”
BackgroundInfluentialBurd, 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
Wang, K., Long, B., Liu, F., Wang, J., Liu, C.-Y., Zhao, B., Zhou, L., Sun, T., Wang, M., Yu, T., et al. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehv713 · Cited by 869 · cited 1×
“Furthermore, cir-ZNF609 [45], mm9_circ_012559 [46], and circRNAs from the human C2H2 zinc finger gene family [47] have also been assumed to function as miRNA sponges.”
BackgroundCircular RNAs: analysis, expression and potential functions
Barrett, S. P., & Salzman, J. (2016) · Development · doi:10.1242/dev.128074 · Cited by 859 · cited 1×
“In addition, circular RNAs (circRNAs) have been recently identified as a relatively large class of ncRNAs, which are widespread and abundant in a variety of eukaryotic organisms and involved in multiple biological processes [3, 4].”
BackgroundTopHat-Fusion: an algorithm for discovery of novel fusion transcripts
Kim, D., & Salzberg, S. L. (2011) · Genome biology · doi:10.1186/gb-2011-12-8-r72 · Cited by 816 · cited 1×
“Also, the TopHat-Fusion algorithm has been designed to detect circRNAs that are derived from gene fusion events [79].”
MethodUsing 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 779
Induction of tumor apoptosis through a circular RNA enhancing Foxo3 activity
Du, W. W., Fang, L., Yang, W., Wu, N., Awan, F. M., Yang, Z., & Yang, B. B. (2016) · Cell Death and Differentiation · doi:10.1038/cdd.2016.133 · Cited by 776
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 · cited 1×
“It was shown that peptides could be translated from ecircRNAs both in vitro and in vivo, when RNA molecules contained the internal ribosomal entry site (IRES) elements or prokaryotic ribosome binding sites [36, 54, 55] (Figure 2(d)).”
BackgroundCircular 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 · cited 1×
“In the last decade, RNA-seq and other nextgeneration sequencing techniques have enabled a significant breakthrough in circRNA discovery, leading to the identification and characterization of a large number of circRNAs in humans and other eukaryotes [9, 10].”
BackgroundOncogenic 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 · cited 1×
“f-circRNA PML/ RARα APL Up NA Promoting cell proliferation, transformation, and tumorigenesis [123]”
BackgroundBachmayr-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
Suzuki, H. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl151 · Cited by 687 · cited 1×
“, RNase R) [9, 31], they may accumulate in the cell with a possible toxic effect.”
BackgroundChen, J., Li, Y., Zheng, Q., Bao, C., He, J. G., Chen, B., Lyu, D., Zheng, B., Xu, Y., Long, Z., et al. (2016) · Cancer Letters · doi:10.1016/j.canlet.2016.12.006 · Cited by 685
Efficient backsplicing produces translatable circular mRNAs
Wang, Y., & Wang, Z. (2014) · RNA · doi:10.1261/rna.048272.114 · Cited by 676 · cited 2×
“However, the regulation process of backsplicing in controlling circRNA production fundamentally differs from that of linear splicing, where the same combinations of splicing regulatory elements and factors have distinct or even opposite activity [18].”
BackgroundThe 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
Memczak, S., Papavasileiou, P., Peters, O., & Rajewsky, N. (2015) · PLoS ONE · doi:10.1371/journal.pone.0141214 · Cited by 639
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 · cited 1×
“Inhibition of the Wnt/β-catenin pathway [104]”
Szabo, L. A., Morey, R. E., Palpant, N. J., Wang, P., Afari, N., Chuan, J., Parast, M. M., Murry, C. E., Laurent, L. C., & Salzman, J. (2015) · Genome biology · doi:10.1186/s13059-015-0690-5 · Cited by 610 · cited 2×
“Among the described circRNA detection tools, which were also compared with regard to their precision and sensitivity, were circRNA_ finder [64], CIRCexplorer [24], DCC [65], find_circ [9], UROBORUS [66], PTESFinder [67], KNIFE [68], CIRI [69], MapSplice [70], segemehl [71], and NCLscan [72].”
MethodCircHIPK3 sponges miR‐558 to suppress heparanase expression in bladder cancer cells
Li, Y., Zheng, F., Xiao, X., Xie, F., Tao, D., Huang, C., Liu, D., Wang, M., Wang, L., Zeng, F., et al. (2017) · EMBO Reports · doi:10.15252/embr.201643581 · Cited by 562
Weng, W., Wei, Q., Toden, S., Yoshida, K., Nagasaka, T., Fujiwara, T., Cai, S., Qin, H., Ma, Y., & Goel, A. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-2541 · Cited by 512
circRNADb: A comprehensive database for human circular RNAs with protein-coding annotations
Chen, X., Han, P., Zhou, T., Guo, X., Song, X., & Li, Y. (2016) · Scientific Reports · doi:10.1038/srep34985 · Cited by 505
Circular RNAs: splicing’s enigma variations
Hentze, M. W., & Preiss, T. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.53 · Cited by 455 · cited 2×
“In addition, some ecircRNAs can store, sort, or localize RBPs and presumably regulate the RBP function by acting as competing elements, in a similar way as they affect miRNA activity [9, 35].”
BackgroundGhosal, S., Das, S., Sen, R., Basak, P., & Chakrabarti, J. (2013) · Frontiers in Genetics · doi:10.3389/fgene.2013.00283 · Cited by 444
Circular RNA biogenesis can proceed through an exon-containing lariat precursor
Barrett, S. P., Wang, P., & Salzman, J. (2015) · eLife · doi:10.7554/elife.07540 · Cited by 443
Wang, Y., Mo, Y., Gong, Z., Yang, X., Yang, M., Zhang, S., Xiong, F., Xiang, B., Zhou, M., Liao, Q., et al. (2017) · Molecular Cancer · doi:10.1186/s12943-017-0598-7 · Cited by 442 · cited 1×
“Current knowledge about the involvement of circRNAs in cancer development and progression is limited, and the role of circRNAs as miRNA sponges has been proposed as the most frequent mechanism of circRNA activity in tumor cells [80].”
BackgroundHsa_circ_0001649: A circular RNA and potential novel biomarker for hepatocellular carcinoma
Qin, M., Liu, G., Huo, X., Tao, X., Sun, X., Ge, Z., Yang, J., Fan, J., Liu, L., & Qin, W. (2016) · Cancer Biomarkers · doi:10.3233/cbm-150552 · Cited by 441
Fang, Y., Xue, J., Shen, Q., Chen, J., & Tian, L. (2012) · Hepatology · doi:10.1002/hep.25576 · Cited by 425 · cited 1×
“miR-7 has been shown to be involved in suppressing melanoma [84], breast cancer [85], glioma [86], gastric cancer [87], liver cancer [88], non-small-cell lung cancer (NSCLC) [89], colorectal cancer [90], and other cancer types.”
BackgroundXie, H., Ren, X., Xin, S., Lan, X.-L., Lu, G.-F., Lin, Y., Yang, S., Zeng, Z., Liao, W., Ding, Y., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.8589 · Cited by 425 · cited 1×
“Hsa_circ_001569 ABCC1 Colorectal Up NA Sponge: miR-145 [99]”
Zhong, Z., Lv, M., & Chen, J. (2016) · Scientific Reports · doi:10.1038/srep30919 · Cited by 409
Biogenesis, identification, and function of exonic circular RNAs
Chen, I., Chen, C., & Chuang, T. (2015) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1294 · Cited by 402
Circular RNAs Co-Precipitate with Extracellular Vesicles: A Possible Mechanism for circRNA Clearance
Lasda, E. L., & Parker, R. (2016) · PLoS ONE · doi:10.1371/journal.pone.0148407 · Cited by 382 · cited 1×
“A study employing three cell lines has shown that the aggregated excessive circRNAs could be effectively eliminated from cells via released vesicles such as exosomes and microvesicles [32].”
BackgroundUsing circular RNA hsa_circ_0000190 as a new biomarker in the diagnosis of gastric cancer
Chen, S., Li, T., Zhao, Q., Xiao, B., & Guo, J. (2017) · Clinica Chimica Acta · doi:10.1016/j.cca.2017.01.025 · Cited by 380
Specific identification and quantification of circular RNAs from sequencing data
Cheng, J., Metge, F., & Dieterich, C. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btv656 · Cited by 372 · cited 2×
“Among the described circRNA detection tools, which were also compared with regard to their precision and sensitivity, were circRNA_ finder [64], CIRCexplorer [24], DCC [65], find_circ [9], UROBORUS [66], PTESFinder [67], KNIFE [68], CIRI [69], MapSplice [70], segemehl [71], and NCLscan [72].”
MethodComprehensive characterization of tissue-specific circular RNAs in the human and mouse genomes
Xia, S., Feng, J. Q., Lei, L., Hu, J., Xia, L., Wang, J., Xiang, Y., Liu, L., Zhong, S., Han, L., et al. (2016) · Briefings in Bioinformatics · doi:10.1093/bib/bbw081 · Cited by 368 · cited 2×
“cn/TSCD/ An integrated database designed for depositing features of human and mouse tissue-specific circRNAs [62] 6 International Journal of Genomics”
BackgroundA comprehensive overview and evaluation of circular RNA detection tools
Zeng, X., Lin, W., Guo, M., & Zou, Q. (2017) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1005420 · Cited by 347 · cited 2×
“In general, these circRNA detection tools can be divided into two categories, based on the different strategies used for circRNA identification, according to the dependency on genome annotation [63].”
MethodCircular RNA-ITCH Suppresses Lung Cancer Proliferation via Inhibiting the Wnt/β-Catenin Pathway
Wan, L., Zhang, L., Fan, K., Cheng, Z., Sun, Q., & Wang, J. (2016) · BioMed Research International · doi:10.1155/2016/1579490 · Cited by 343 · cited 1×
“Inhibition of the Wnt/β-catenin pathway [106]”
CircNet: a database of circular RNAs derived from transcriptome sequencing data
Liu, Y., Li, J., Sun, C.-H., Andrews, E. H., Chao, R.-F., Lin, F.-M., Weng, S.-L., Hsu, S., Huang, C., Cheng, C., et al. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv940 · Cited by 342 · cited 3×
“ZEB1 Lung Down NA Sponge: miR-200a-3p [58] Circ-ZEB1.”
BackgroundInfluentialShang, X., Li, G., Liu, H., Li, T., Liu, J., Zhao, Q., & Wang, C. (2016) · Medicine · doi:10.1097/md.0000000000003811 · Cited by 333
Liang, H., Zhang, X.-Z., Liu, B., Jia, G., & Li, W. (2017) · PubMed Central · Cited by 329
Yang, W., Du, W. W., Li, X., Yee, A., & Yang, B. B. (2015) · Oncogene · doi:10.1038/onc.2015.460 · Cited by 316 · cited 2×
“However, among the two, circ-Foxo3 appeared to possess a stronger sponging effect on these miRNAs [95].”
BackgroundNovel classes of non-coding RNAs and cancer
Šáňa, J., Vychytilova‐Faltejskova, P., Svoboda, M., & Slabý, O. (2012) · Journal of Translational Medicine · doi:10.1186/1479-5876-10-103 · Cited by 314 · cited 2×
“The small ncRNAs include microRNAs (miRNAs), small nuclear RNAs (snRNAs), PIWI-interacting RNAs (piRNAs), small interfering RNAs (siRNAs), small nucleolar RNAs (snoRNAs), and others [1], whereas lncRNAs comprise long intergenic ncRNAs (lincRNAs), intronic ncRNAs, macroRNAs, sense ncRNA, antisense RNAs, and others [2].”
BackgroundCircular RNA profile in gliomas revealed by identification tool UROBORUS
Song, X., Zhang, N., Han, P., Moon, B.-S., Lai, R., Wang, K., & Lu, W. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw075 · Cited by 307 · cited 2×
“Among the described circRNA detection tools, which were also compared with regard to their precision and sensitivity, were circRNA_ finder [64], CIRCexplorer [24], DCC [65], find_circ [9], UROBORUS [66], PTESFinder [67], KNIFE [68], CIRI [69], MapSplice [70], segemehl [71], and NCLscan [72].”
MethodXu, L., Zhang, M., Zheng, X., Yi, P., Lan, C., & Xu, M. (2016) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-016-2256-7 · Cited by 303
Liu, Q., Zhang, X., Hu, X., Dai, L., Fu, X., Zhang, J., & Ao, Y. (2016) · Scientific Reports · doi:10.1038/srep22572 · Cited by 302
Yao, Z., Luo, J., Hu, K., Lin, J., Huang, H., Wang, Q., Zhang, P., Xiong, Z., He, C., Huang, Z., et al. (2017) · Molecular Oncology · doi:10.1002/1878-0261.12045 · Cited by 301
cir-ITCH Plays an Inhibitory Role in Colorectal Cancer by Regulating the Wnt/β-Catenin Pathway
Huang, G., Zhu, H., Shi, Y., Wu, W., Cai, H., & Chen, X. (2015) · PLoS ONE · doi:10.1371/journal.pone.0131225 · Cited by 298 · cited 1×
“Colorectal Down NA Sponge: miR-7, miR-20a Inhibition of the Wnt/β-catenin pathway [105]”
BackgroundZhang, Y., Liu, H., Li, W., Yu, J., Li, J., Shen, Z., Ye, G., Qi, X., & Li, G. (2017) · Aging · doi:10.18632/aging.101254 · Cited by 294 · cited 1×
“CircRNA_100269 LPHN2 Gastric Down NA Sponge: miR-630 [116]”
Circular RNAs in cancer: an emerging key player
Dong, Y., He, D., Peng, Z., Peng, W., Shi, W., Wang, J., Li, B., Zhang, C., & Duan, C. (2017) · Journal of Hematology & Oncology · doi:10.1186/s13045-016-0370-2 · Cited by 290 · cited 1×
“Generally, circRNAs can be generated by canonical and noncanonical splicing [20].”
BackgroundA multi-split mapping algorithm for circular RNA, splicing, trans-splicing and fusion detection
Hoffmann, S., Otto, C., Doose, G., Andrea Tanzer, A., Langenberger, D., Christ, S., Kunz, M., Holdt, L. M., Teupser, D., Hackermüller, J., et al. (2014) · Genome biology · doi:10.1186/gb-2014-15-2-r34 · Cited by 270 · cited 1×
“Among the described circRNA detection tools, which were also compared with regard to their precision and sensitivity, were circRNA_ finder [64], CIRCexplorer [24], DCC [65], find_circ [9], UROBORUS [66], PTESFinder [67], KNIFE [68], CIRI [69], MapSplice [70], segemehl [71], and NCLscan [72].”
MethodXia, W., Qiu, M., Chen, R., Wang, S., Leng, X., Wang, J., Xu, Y., Hu, J., Dong, G., Xu, P. L., et al. (2016) · Scientific Reports · doi:10.1038/srep35576 · Cited by 269 · cited 1×
“8 Promoting cell proliferation and migration [107]”
Huang, M., Zhong, Z., Lv, M., Shu, J. S., Tian, Q., & Chen, J. (2016) · Oncotarget · doi:10.18632/oncotarget.9706 · Cited by 259 · cited 1×
“CircMYLK MYLK Bladder Up NA Sponge: miR-29a-3p [109]”
BackgroundCircular RNAs as potential biomarkers for cancer diagnosis and therapy.
Wang, F., Nazarali, A. J., & Ji, S. (2016) · PubMed Central · Cited by 254
Over-expression of CircRNA_100876 in non-small cell lung cancer and its prognostic value
Yao, J., Zhao, S., Liu, Q., Lv, M., Zhou, D., Zi-jun, L., & Nan, K. (2017) · Pathology - Research and Practice · doi:10.1016/j.prp.2017.02.011 · Cited by 249 · cited 1×
“2 Sponge: miR-136 [133] 8 International Journal of Genomics”
BackgroundZhang, X., Xu, L., & Wang, F. (2017) · Cell Biology International · doi:10.1002/cbin.10826 · Cited by 241 · cited 1×
“Hsa_circ_0020397 DOCK1 Colorectal Up NA Sponge: miR-138 [117]”
Zheng, L., Li, J., Wu, J., Sun, W., Liu, S., Wang, Z., Zhou, H., Yang, J., & Qu, L. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv1273 · Cited by 226 · cited 2×
“The platform also provides an integrative, interactive, and versatile web graphical interface to display multidimensional data and facilitates transcriptomic research and the discovery of novel ncRNAs [61].”
BackgroundMethodZhao, X., Dou, W., He, L., Liang, S., Tie, J., Liu, C., Li, T., Lu, Y., Mo, P., Shi, Y., et al. (2012) · Oncogene · doi:10.1038/onc.2012.156 · Cited by 220 · cited 1×
“miR-7 has been shown to be involved in suppressing melanoma [84], breast cancer [85], glioma [86], gastric cancer [87], liver cancer [88], non-small-cell lung cancer (NSCLC) [89], colorectal cancer [90], and other cancer types.”
BackgroundThe complexity of the translation ability of circRNAs
Granados-Riveron, J. T., & Aquino‐Jarquín, G. (2016) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2016.07.009 · Cited by 218 · cited 1×
“It was shown that peptides could be translated from ecircRNAs both in vitro and in vivo, when RNA molecules contained the internal ribosomal entry site (IRES) elements or prokaryotic ribosome binding sites [36, 54, 55] (Figure 2(d)).”
BackgroundTTBK2 circular RNA promotes glioma malignancy by regulating miR-217/HNF1β/Derlin-1 pathway
Zheng, J., Liu, X., Xue, Y., Gong, W., Ma, J., Xi, Z., Que, Z., & Liu, Y. (2017) · Journal of Hematology & Oncology · doi:10.1186/s13045-017-0422-2 · Cited by 216 · cited 1×
“Circ-TTBK2 TTBK2 Glioma Up NA Sponge: miR-217 [121]”
microRNA-7 is a novel inhibitor of YY1 contributing to colorectal tumorigenesis
Zhang, N., Li, X., Wu, C. W., Dong, Y., Cai, M., Mok, M. T. S., Wang, H., Chen, J., Ng, S. S. M., Chen, M., et al. (2012) · Oncogene · doi:10.1038/onc.2012.526 · Cited by 213 · cited 1×
“miR-7 has been shown to be involved in suppressing melanoma [84], breast cancer [85], glioma [86], gastric cancer [87], liver cancer [88], non-small-cell lung cancer (NSCLC) [89], colorectal cancer [90], and other cancer types.”
BackgroundDecreased expression of hsa_circ_001988 in colorectal cancer and its clinical significances.
Wang, X., Zhang, Y., Huang, L., Zhang, J., Pan, F., Li, B., Yan, Y., Jia, B., Liu, H., Li, S., et al. (2015) · PubMed Central · Cited by 210
IRESite—a tool for the examination of viral and cellular internal ribosome entry sites
Mokrejš, M., Mašek, T., Vopálenský, V., Hlubuček, P., Delbos, P., & Pospíšek, M. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp981 · Cited by 207 · cited 2×
“In addition, several integrated tools aimed to identify circRNAs with a protein-coding potential have been developed, including CircPro [74], IRESite [75], CPAT [76], Pfam 31.0 [77], PhyloCSF [78], and ORF Finder from the NCBI database.”
MethodInfluentialYang, P., Qiu, Z., Jiang, Y., Dong, L., Yang, W., Gu, C., Li, G., & Zhu, Y. T. (2016) · Oncotarget · doi:10.18632/oncotarget.11523 · Cited by 199 · cited 1×
“cZNF292 ZNF292 Glioma Up NA Promoting cell proliferation and tube formation [122]”
BackgroundKong, X., Li, G., Yuan, Y., He, Y., Wu, X., Zhang, W., Wu, Z., Chen, T., Wu, W., Lobie, P. E., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0041523 · Cited by 195 · cited 1×
“miR-7 has been shown to be involved in suppressing melanoma [84], breast cancer [85], glioma [86], gastric cancer [87], liver cancer [88], non-small-cell lung cancer (NSCLC) [89], colorectal cancer [90], and other cancer types.”
BackgroundCircular RNA: a novel biomarker for progressive laryngeal cancer.
Xuan, L., Qu, L., Zhou, H., Wang, P., Yu, H., Wu, T., Wang, X., Li, Q., Tian, L., Liu, M., et al. (2016) · PubMed Central · Cited by 193
Xiong, S., Zheng, Y., Jiang, P., Liu, R., Liu, X., & Chu, Y. (2011) · International Journal of Biological Sciences · doi:10.7150/ijbs.7.805 · Cited by 192 · cited 7×
“CircRNA_100876 was significantly upregulated in NSCLC tissues, when compared to their paired adjacent nontumorous tissues (n = 101), and its elevated levels closely correlated with lymph node metastasis and advanced tumor staging in NSCLC [133].”
BackgroundInfluentialFu, L., Yao, T. S., Chen, Q., Mo, X., Hu, Y., & Guo, J. (2017) · Oncotarget · doi:10.18632/oncotarget.16881 · Cited by 178
Peng, L., Chen, G., Zhu, Z., Shen, Z., Du, C., Zang, R., Su, Y., Xie, H., Li, H., Xu, X., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.13656 · Cited by 173 · cited 1×
“Furthermore, cir-ZNF609 [45], mm9_circ_012559 [46], and circRNAs from the human C2H2 zinc finger gene family [47] have also been assumed to function as miRNA sponges.”
BackgroundSilencing CDR1as inhibits colorectal cancer progression through regulating microRNA-7
Tang, W., Ji, M., He, G., Yang, L., Niu, Z., Jian, M., Wei, Y., Ren, L., & Xu, J. (2017) · OncoTargets and Therapy · doi:10.2147/ott.s131597 · Cited by 167 · cited 2×
“Similarly, elevated expression of ciRS-7 was determined in colorectal cancer tissues, when compared to those of the adjacent normal mucosa, which was positively associated with tumor size, T stage, lymph node metastasis, and poor overall survival [92].”
BackgroundInverted 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 · cited 1×
“However, in adult testes, the circular form of Sry is expressed, with its circularization being dictated by promotor usage and dependent on intron pairing-driven circularization [43, 44].”
BackgroundGuo, J., Li, J., Zhu, C., Feng, W.-T., Shao, J.-X., Wan, L., Huang, M., & He, J. (2016) · OncoTargets and Therapy · doi:10.2147/ott.s123220 · Cited by 153 · cited 1×
“0 Promoting cell proliferation, invasion, and migration [118]”
BackgroundCircular 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 · cited 1×
“It was shown that peptides could be translated from ecircRNAs both in vitro and in vivo, when RNA molecules contained the internal ribosomal entry site (IRES) elements or prokaryotic ribosome binding sites [36, 54, 55] (Figure 2(d)).”
BackgroundReduced expression of circ RNA hsa_circ_0003159 in gastric cancer and its clinical significance
Tian, M., Chen, R., Li, T., & Xiao, B. (2017) · Journal of Clinical Laboratory Analysis · doi:10.1002/jcla.22281 · Cited by 148
dos Santos, G. A., Kats, L. M., & Pandolfi, P. P. (2013) · The Journal of Experimental Medicine · doi:10.1084/jem.20131121 · Cited by 147
Lariat intronic RNAs in the cytoplasm of Xenopus tropicalis oocytes
Talross, G. J. S., & Gall, J. G. (2014) · RNA · doi:10.1261/rna.045781.114 · Cited by 147 · cited 1×
“During back-splicing, the two elements bind into a lariatlike intermediate, containing the excised exons and introns, and are cut out by the spliceosome [17, 30].”
BackgroundUsing artificial microRNA sponges to achieve microRNA loss-of-function in cancer cells
Tay, F. C., Lim, J. K., Zhu, H., Hin, L. C., & Wang, S. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.05.010 · Cited by 139 · cited 1×
“Overall, when compared to linear miRNA sponges, circRNAs have proven themselves as more stable and therefore more effective [48, 49].”
BackgroundChuang, T., Wu, C.-S., Chen, C.-Y., Hung, L.-Y., Chiang, T.-W., & Yang, M.-Y. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv1013 · Cited by 125 · cited 2×
“Among the described circRNA detection tools, which were also compared with regard to their precision and sensitivity, were circRNA_ finder [64], CIRCexplorer [24], DCC [65], find_circ [9], UROBORUS [66], PTESFinder [67], KNIFE [68], CIRI [69], MapSplice [70], segemehl [71], and NCLscan [72].”
MethodLiang, Y., Wang, W., Fang, C., Raj, S. S., Hu, W.-M., Li, Q.-W., & Zhou, Z.-W. (2016) · Oncotarget · doi:10.18632/oncotarget.10391 · Cited by 125
MicroRNA-7: a promising new target in cancer therapy
Zhao, J., Tao, Y., Zhou, Y., Qin, N., Chen, C., Tian, D., & Xu, L. (2015) · Cancer Cell International · doi:10.1186/s12935-015-0259-0 · Cited by 120 · cited 1×
“There is emerging evidence that miR-7 can directly downregulate oncogenes in a variety of cancers [82, 83].”
BackgroundDysregulated miR-671-5p / CDR1-AS / CDR1 / VSNL1 axis is involved in glioblastoma multiforme
Barbagallo, D., Condorelli, A. G., Ragusa, M., Salito, L., Sammito, M., Banelli, B., Caltabiano, R., Barbagallo, G. M. V., Zappalà, A., Battaglia, R., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.6621 · Cited by 118
Fu, L., Chen, Q., Yao, T. S., Li, T., Ying, S., Hu, Y., & Guo, J. (2017) · Oncotarget · doi:10.18632/oncotarget.16709 · Cited by 118
Decreased Expression of Hsa_circ_00001649 in Gastric Cancer and Its Clinical Significance
Li, W., Song, Y., Zhang, H., Zhou, Z., Xie, X., Zeng, Q., Guo, K., Wang, T., Xia, P., & Chang, D. (2017) · Disease Markers · doi:10.1155/2017/4587698 · Cited by 109
CircPro: an integrated tool for the identification of circRNAs with protein-coding potential
Meng, X., Chen, Q., Zhang, P., & Chen, M. (2017) · Bioinformatics · doi:10.1093/bioinformatics/btx446 · Cited by 106 · cited 2×
“In addition, several integrated tools aimed to identify circRNAs with a protein-coding potential have been developed, including CircPro [74], IRESite [75], CPAT [76], Pfam 31.0 [77], PhyloCSF [78], and ORF Finder from the NCBI database.”
MethodInfluentialmiRNA-7-5p inhibits melanoma cell migration and invasion
Giles, K. M., Brown, R. A. M., Epis, M. R., Kalinowski, F. C., & Leedman, P. J. (2012) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2012.11.086 · Cited by 93 · cited 1×
“miR-7 has been shown to be involved in suppressing melanoma [84], breast cancer [85], glioma [86], gastric cancer [87], liver cancer [88], non-small-cell lung cancer (NSCLC) [89], colorectal cancer [90], and other cancer types.”
BackgroundDecreased expression of hsa_circ_0001895 in human gastric cancer and its clinical significances
Shao, Y., Chen, L., Lu, R., Zhang, X., Xiao, B., Ye, G., & Guo, J. (2017) · Tumor Biology · doi:10.1177/1010428317699125 · Cited by 89
Circular RNA hsa-circ-0016347 promotes proliferation, invasion and metastasis of osteosarcoma cells
Jin, H., Jin, X., Zhang, H., & Wang, W. (2017) · Oncotarget · doi:10.18632/oncotarget.16104 · Cited by 84
Identification of differentially expressed circular RNAs in human colorectal cancer
Zhang, P., Zuo, Z., Shang, W., Wu, A., Bi, R., Wu, J., Li, S., Sun, X., & Jiang, L. (2017) · Tumor Biology · doi:10.1177/1010428317694546 · Cited by 82 · cited 2×
“6 Sponge: miR-511-5p, miR-130b-5p, miR-642a-5p, miR-532-3p, miR-329-5p [131]”
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Metadata
- Authors
- Bolha, L., Ravnik-Glavač, M., & Glavač, D.
- Affiliations
- University of Ljubljana (SI)
- Department of Molecular Genetics, Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
- Corresponding author
- Glavač, Damjan
- Venue
- International Journal of Genomics
- Publisher
- Wiley
- Published
- 2017
- Volume
- 2017
- Pages
- 1-19
- ISSN
- 2314-436X (ISSN-L)
- 2314-4378
- PMC
- PMC5733622
- OpenAlex
- W2771561127
- Cited by
- 166
- References
- 150
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 22 · 2023: 17 · 2022: 21 · 2021: 21 · 2020: 38 · 2019: 20 · 2018: 15
- FWCI
- 1.89
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- International Journal of Genomics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Circular RNAs in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- circular RNA, circRNA biogenesis, back-splicing, non-coding RNA, microRNA sponge, cap-independent translation, circRNA stability, tumor markers, cancer diagnosis, cancer prognosis
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