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Circular RNAs are long-lived and display only minimal early alterations in response to a growth factor
Open accessAbstract
Circular RNAs (circRNAs) are widespread circles of non-coding RNAs with largely unknown function. Because stimulation of mammary cells with the epidermal growth factor (EGF) leads to dynamic changes in the abundance of coding and non-coding RNA molecules, and culminates in the acquisition of a robust migratory phenotype, this cellular model might disclose functions of circRNAs. Here we show that circRNAs of EGF-stimulated mammary cells are stably expressed, while mRNAs and microRNAs change within minutes. In general, the circRNAs we detected are relatively long-lived and weakly expressed. Interestingly, they are almost ubiquitously co-expressed with the corresponding linear transcripts, and the respective, shared promoter regions are more active compared to genes producing linear isoforms with no detectable circRNAs. These findings imply that altered abundance of circRNAs, unlike changes in the levels of other RNAs, might not play critical roles in signaling cascades and downstream transcriptional networks that rapidly commit cells to specific outcomes.
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“endogenous circRNAs lack the free ends necessary for exonuclease-mediated degradation, rendering them resistant to several mechanisms of RNA turnover and granting them extended lifespans as compared to their linear mRNA counterparts2, 9.”
From Engineering circular RNA for potent and stable translation in eukaryotic cells (2018) · cites this paper as [9]
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Mellios, N., Papageorgiou, G., Gorgievski, V., Maxson, G., Hernandez, M., Otero, M. P., Varangis, M., Dell’Orco, M., Perrone‐Bizzozero, N. I., & Tzavara, E. T. (2024) · Research Square · doi:10.21203/rs.3.rs-3547375/v1 · Cited by 11
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“These circRNAs exhibit remarkable stability, with half-lives ranging from 18.8 to 23.7 hours, significantly longer than the mean of 4.0 to 7.4 hours observed for their linear RNA counterparts [2].”
InfluentialYang, J., Fan, Q., Wang, Y., Liu, Y., Xu, X., Liang, Y., Xie, J. L., Li, J., Ai, F., Cao, Y. B., et al. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2025.1525779 · Cited by 10
“The utility of circRNAs as diagnostic biomarkers is underscored by several key attributes: First, stability: CircRNAs exhibit notable stability and are conserved across species within cells, facilitating their detection (153, 154).”
Circular RNAs as disease modifiers of complex neurologic disorders
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Epigenetic regulation of autophagy in coronavirus disease 2019 (COVID-19)
Behrouj, H., Vakili, O., Sadeghdoust, A., Aligolighasemabadi, N., Khalili, P., Zamani, M., & Mokarram, P. (2022) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2022.101264 · Cited by 11
“Circular RNAs (circRNAs) are another form of noncoding RNAs that are usually expressed in tissues and body fluids [163].”
The potential of CircRNA1002 as a biomarker in hepatitis B virus-related hepatocellular carcinoma
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MicroRNAs induced by Listeria monocytogenes and their role in cells
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“Initial studies have shown that the abnormal expression of specific circRNAs in OS can affect cell proliferation, invasion, and multidrug resistance (Wang et al. 2020b, 2021; Enuka et al. 2016).”
BackgroundEmerging role of microRNAs as regulators of protein kinase C substrate MARCKS and MARCKSL1 in cancer
Yadav, V. K., Jena, M. K., Parashar, G., Parashar, N. C., Joshi, H., Ramniwas, S., & Tuli, H. S. (2023) · Experimental Cell Research · doi:10.1016/j.yexcr.2023.113891 · Cited by 10
Circular RNAs and Its Biological Functions in Health and Disease
Sağlam, A. S. Y., Alp, E., & Önen, H. İ. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.88764 · Cited by 10
Current research on circular RNAs and their potential clinical implications in breast cancer
Liu, D., & Fang, L. (2021) · Cancer Biology and Medicine · doi:10.20892/j.issn.2095-3941.2020.0275 · Cited by 11
Circular noncoding RNA hsa_circ_0005986 as a prognostic biomarker for hepatocellular carcinoma
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Aherrahrou, R., Lue, D., & Civelek, M. (2022) · Human Genetics and Genomics Advances · doi:10.1016/j.xhgg.2022.100164 · Cited by 10
“Because of their lack of ends, circRNAs are protected from exonucleases and have a longer lifespan than their linear counterparts.(7) CircANRIL,(8) circACTA2,(9) circLRP6,(10) circSFMBT2,(11) and circMAP3K5(12) are involved in SMC migration, proliferation, and phenotypic modulation.”
BackgroundInsights Into circRNAs: Functional Roles in Lung Cancer Management and the Potential Mechanisms
Feng, B. C., Zhou, H., Wang, T., Lin, X., Lai, Y., Chu, X., & Wang, R. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.636913 · Cited by 10
“In detail, circRNAs can strengthen interactions between proteins through direct binding to both of them (Huang S. et al., 2019) or just one of them (Fang et al., 2018), or dissociate interactions between proteins originally combined together by direct binding to both of them (Fang et al., 2019).”
BackgroundCircular RNA-EPHB4 As A Potential Biotarget In Colorectal Cancer: A Preliminary Analysis
Nasir, S. N., Ishak, M., Mutalib, N. A., Jamal, R., & Abu, N. (2022) · Progress In Microbes & Molecular Biology · doi:10.36877/pmmb.a0000249 · Cited by 9
“Apart from that, circRNAs are known to be more stable and are have longer half-lives([6,7]), thus making them ideal targets for biomarker identification.”
BackgroundPapageorgiou, G., Amoah, S. K., Pierotti, C. E., Otero, M. P., Eckel, S. E., Coffey, K., Allan, A. M., Caldwell, K. K., & Mellios, N. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1087950 · Cited by 10
“CircRNAs are created by the back-splicing of a single-stranded linear transcript whose ends are covalently bound and are known to be much more stable than mRNAs, with a half-life time of days to a week (Jeck et al., 2013; Memczak et al., 2013; You et al., 2015; Enuka et al., 2016).”
BackgroundYin, D., Li, Y., Feng, X., Zhai, X., Mei, H., Liu, J., & Chen, Y. (2024) · Molecular Biotechnology · doi:10.1007/s12033-023-01040-2 · Cited by 9
“CircRNAs lack 5 ′ or 3 ′ polarities structure and thus are more resistant to RNase degradation [14].”
CircRNAs in the tumor microenvironment: new frontiers in cancer progression and therapy
Guo, Y., Gong, Y., Wu, M., Ji, M., Xie, F., Chen, H., Niu, H., & Tang, C. (2025) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2025.104754 · Cited by 9
Dual roles of DEAD-box RNA helicase Brr2 in genome stability regulation
Chen, X., You, J., Ma, Q., Lin, J., Ji, Y., Shi, L., Song, Z., Su, R. J., Shan, G., & Huang, C. (2025) · Nature Communications · doi:10.1038/s41467-025-64174-8 · Cited by 9
“Moreover, considering that the half-lives of linear RNAs are much shorterthanthatofcircRNAs 41 – 43 ,weperformedActDtreatment(0.5,1 and 4 hr) to reduce the overall abundance of linear mRNAs in cells priortoS9.”
InfluentialBaiddou, C., Knidiri, M., Ghazi, B., Obaid, A. A. A., Hamdi, S., & Errafii, K. (2026) · Non-coding RNA Research · doi:10.1016/j.ncrna.2025.12.005 · Cited by 10
“According to a study conducted by Enuka et al., circRNAs exhibit a long duration of stability, with longevity 2.5 times greater than linear RNAs within mammary cells [24].”
InfluentialHints From the Cellular Functions to the Practical Outlook of Circular RNAs
Yesharim, L., Mojbafan, M., & Abiri, M. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.679446 · Cited by 9
“5 times more than their linear counterpart, and this stability can last up to 48 h in cells (Jeck et al., 2013; Enuka et al., 2015).”
BackgroundZhao, Y., Jaber, V. R., & Lukiw, W. J. (2022) · Frontiers in Drug Discovery · doi:10.3389/fddsv.2022.983030 · Cited by 9
“seems fitting that novel therapeutic strategies involving multiple regulatory components should be preferred over the classical single-target therapeutic approach (Enuka et al., 2016; Grabowska-Pyrzewicz et al., 2021; Walgrave et al., 2021).”
BackgroundSelf-restricted circular RNA circSOX2 suppressed the malignant progression in SOX2-amplified LUSC
Liang, Y., Wang, N., Zhang, Y., Jiang, W., Chen, F., Feng, Y., Ma, H., Jiang, F., & Dong, G. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-05288-5 · Cited by 9
“CircSOX2 acted as a self-restricted circRNA of the SOX2 gene in SOX2-amplified LUSC The localization of circRNAs partially indicates the potential regulatory mechanism in cells.”
BackgroundInfluentialCheng, L., Liu, Z., & Xia, J. (2022) · Molecular Biology Reports · doi:10.1007/s11033-022-07949-2 · Cited by 9
Cheng, Y., Xu, S.-M., Takenaka, K., Lindner, G., Curry‐Hyde, A., & Janitz, M. (2023) · Gene · doi:10.1016/j.gene.2023.147568 · Cited by 11
Tuerdimaimaiti, D., Abuduaini, B., Kang, S., Jiao, J., Li, M., Madeniyati, W., Baihetinisha, T., Aili, G., Tuerhong, R., & Kulaxi, A. (2023) · Journal of Inflammation · doi:10.1186/s12950-023-00355-w · Cited by 9
“In general, mechanisms underlying the expression of genes in sepsis may involve circular RNAs (circRNAs) [20], a stable form of non-coding RNA [21]; often these act as sponges for miRNA [22].”
BackgroundThe Emerging Role of Circular RNAs in Prostate Cancer: A Systematic Review
Chao, F., Wang, S., Zhang, C., Han, D., Xu, G., & Chen, G. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.681163 · Cited by 9
Ren, Z., Yang, Q., Guo, J., Huang, H., Li, B., Yang, Z., & Tian, X. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.714601 · Cited by 9
CircRNAs in Malignant Tumor Radiation: The New Frontier as Radiotherapy Biomarkers
Wu, X., Wu, J., Wang, L., Yang, W., Wang, B., & Yang, H. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.854678 · Cited by 9
de Amorim, M. G., Branco, G. P., Valieris, R., Tarcitano, E., da Silva, I. T., de Araújo, L. F., Nunes, D. N., & Dias‐Neto, E. (2019) · Pharmacogenomics · doi:10.2217/pgs-2018-0182 · Cited by 9
Cai, W., Li, J.-T., & Su, J. (2021) · Hellenic Journal of Cardiology · doi:10.1016/j.hjc.2021.06.007 · Cited by 9
Circulating Circles Predict Postoperative Atrial Fibrillation
Reckman, Y. J., & Creemers, E. E. (2018) · Journal of the American Heart Association · doi:10.1161/jaha.117.008261 · Cited by 10
“Because of their circular form, circRNAs are protected from ribonucleases and have greater stability than their linear counterparts.(8) In the heart alone, thousands of different circRNAs are expressed.”
BackgroundSynergically enhanced anti-tumor immunity of in vivo CAR by circRNA vaccine boostingPreprint
Wang, Y., Lin, L., Wang, X., Li, J., Yin, J., Gao, F., Liao, X., Zhang, C., Yin, Q., Zhao, C., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.07.05.600312 · Cited by 9
“Unlike the linear conformation of mRNA, circular RNAs (circRNAs) are covalently closed circular RNA molecules that are more stable than linear mRNAs in mammalian cells 12-14 .”
BackgroundKim, S. S., Ham, S., Boo, S. H., Lee, D., Min, H., Kang, E., Haque, R., Lee, H., Jung, Y., Kwon, S., et al. (2026) · Molecular Cell · doi:10.1016/j.molcel.2026.01.031 · Cited by 8
Circular RNA as emerging precision therapeutics: from RNA regulation to peptide translation
Wu, N., Amalraj, J., & Yang, B. B. (2026) · Precision Clinical Medicine · doi:10.1093/pcmedi/pbag011 · Cited by 9
“Within this setting, circRNAs stand out due to their highly specific expression patterns and exceptional molecular stability, which allow reliable detection in tissues and biofluids and support their use as precise biomarkers [ 5 , 6 , 8 ].”
Circular RNAs in Hedgehog Signaling Activation and Hedgehog-Mediated Medulloblastoma Tumors
Azatyan, A., Zhang, S., Darabi, A., Siesjö, P., Wang, T., & Zaphiropoulos, P. G. (2021) · Cancers · doi:10.3390/cancers13205138 · Cited by 8
“In fact, it has been previously reported that unlike the rapid changes exhibited by mRNAs and miRNAs, the expression levels of circRNAs in MCF10A mammary cells were minimally altered following a 4-h stimulation by epidermal growth factor [38], while a 21-day TGF-β treatment of epithelial cells resulted in major circRN…”
BackgroundBang, D., Gu, J., Park, J., Jeong, D., Koo, B., Yi, J., Shin, J., Jung, I., Kim, S., & Lee, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911498 · Cited by 8
“5 times more stable than their linear counterparts [23].”
BackgroundEmerging roles of circular RNAs in cancer therapy-induced cardiotoxicity
Cheng, Z., Qin, W., Li, S., Shao, S.-J., & Liu, B. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2023.1152436 · Cited by 8
“Remarkably, once produced, most circRNAs are very stable, as they are not only resistant to degradation caused by the linear RNA decay machinery, but also have a longer half-life compared to their cognate linear RNAs (30).”
BackgroundDiagnostic and prognostic role of circRNAs in pancreatic cancer: a meta-analysis
Zhao, R., Han, Z., Zhou, H., Xue, Y., Chen, X., & Cao, X. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1174577 · Cited by 8
“The stability of its function is determined by its closed ring structure (26).”
BackgroundLi, Y., Yang, Z., Zeng, M., Wang, Y., Chen, X., Li, S., Zhao, X., & Sun, Y. (2023) · Journal of Obstetrics and Gynaecology · doi:10.1080/01443615.2023.2228894 · Cited by 8
“Due to a lack of free ends, circRNAs are more stable and resistant to RNases than linear RNAs (Suzuki et al. , 2006, Enuka et al. , 2016).”
BackgroundBlood RNA-Seq profiling reveals a set of circular RNAs differentially expressed in frail individuals
Iparraguirre, L., Alberro, A., Iñiguez, S. G., Muñoz‐Culla, M., Vergara, I., Matheu, A., & Otaegui, D. (2023) · Immunity & Ageing · doi:10.1186/s12979-023-00356-6 · Cited by 8
“stability and longer half-life compared to linear RNAs [10], which eases their detection and reduces the impact of preanalytical factors during sample collection and storage.”
BackgroundMohammadi, M. M., Rismanchi, H., Esmailzadeh, S., Farahani, A., Hedayati, N., Alimohammadi, M., Mafi, A., Farahani, N., & Hushmandi, K. (2024) · Non-coding RNA Research · doi:10.1016/j.ncrna.2024.05.005 · Cited by 9
“CircRNAs, most likely due to their low abundance and high stability, are involved in long-term processes such as differentiation rather than highly dynamic ones such as cell proliferation or migration [81].”
BackgroundEngineering circular RNA for molecular and metabolic reprogramming
Sharma, N. K., Dwivedi, P., Bhushan, R., Maurya, P. K., Kumar, A., & Dakal, T. C. (2024) · Functional & Integrative Genomics · doi:10.1007/s10142-024-01394-z · Cited by 8
“This unique feature confers resistance to various RNA turnover mechanisms, resulting in prolonged lifespans compared to their linear mRNA counterparts (Chen and Yang 2015; Enuka et al. 2016).”
InfluentialCircular RNA Profile in Atherosclerotic Disease: Regulation during ST-Elevated Myocardial Infarction
Holme, F. A., Huse, C., Kong, X. Y., Broch, K., Gullestad, L. L., Anstensrud, A. K., Andersen, G. Ø., Amundsen, B. H., Kleveland, O., Quiles‐Jiménez, A., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25169014 · Cited by 8
“Levels of circRNAs vary at slow rates and are thought to be affected minimally by acute events [5].”
BackgroundInfluentialCellular functions and biomedical applications of circular RNAs
Zhang, Z., & Wang, Z. (2024) · Acta Biochimica et Biophysica Sinica · doi:10.3724/abbs.2024241 · Cited by 9
“Compared with linear RNAs, circular RNAs are more resistant to cleavage by RNA exonucleases due to a lack of free ends and thus are generally more stable in cells [8,10], which is desirable for the development of circRNA - based drugs.”
Bibliometric Analysis of Global Circular RNA Research Trends from 2007 to 2018.
Wu, R., Guo, F., Wang, C., Qian, B., Shen, F., Huang, F., & Xu, W. (2021) · PubMed Central · doi:10.22074/cellj.2021.7143 · Cited by 8
“Meanwhile, circRNAs are more stable, even when treated with RNase R (7).”
BackgroundLi, F., Lyu, J., Yang, Y., Yang, Q., Santos, C., & Yang, B. B. (2022) · Advanced Genetics · doi:10.1002/ggn2.202200019 · Cited by 8
Roles of circular RNAs in the pathogenesis and treatment of pancreatic cancer
Seimiya, T., Otsuka, M., & Fujishiro, M. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.1023332 · Cited by 8
Circular RNAs in extracellular vesicles: Promising candidate biomarkers for schizophrenia
Chuang, G., Lv, H., Bai, Y., Guo, M., Li, P., Tong, S., & He, K. (2023) · Frontiers in Genetics · doi:10.3389/fgene.2022.997322 · Cited by 8
“They are relatively stable molecules with a longer half-life and resistance to degradation than other RNA molecules (Enuka et al., 2016).”
BackgroundLiu, J., Yu, Q., & Yang, X. (2023) · Thoracic Cancer · doi:10.1111/1759-7714.15138 · Cited by 7
Lu, P., Wu, J., & Zhang, W. (2024) · Analytical Biochemistry · doi:10.1016/j.ab.2024.115628 · Cited by 7
CircRNA-mediated regulation of cardiovascular disease
Cheng, K., Wang, S., Lan, T., Mao, Z.-J., Xu, Y., Shen, Q., & Zeng, X. (2024) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2024.1411621 · Cited by 7
“This absence results in circRNAs having longer half-lives (19 – 24 h) compared to their linear counterparts (4 – 7 h) that share the same nucleotide sequence (12).”
Transcriptome‐wide analysis of circRNA and RBP profiles and their molecular relevance for GBM
Latowska-Lysiak, J., Zarębska, Ż., Sajek, M. P., Grabowska, A., Buratin, A., Głodowicz, P., Misiorek, J. O., Kuczyński, K., Bortoluzzi, S., Żywicki, M., et al. (2025) · Molecular Oncology · doi:10.1002/1878-0261.70005 · Cited by 8
“Due to their intrinsic resistance to exonuclease cleavage, cir-cRNAs have a longer half-life in comparison to their linear counterparts making them promising cancer biomarkers [8 – 15].”
Role of non-coding RNA-regulated ferroptosis in colorectal cancer
Zhao, Y., Liu, J., Wang, S., & Li, X. (2025) · Cell Death Discovery · doi:10.1038/s41420-025-02606-6 · Cited by 9
“Unlike common linear RNAs, the closed-loop structure of circRNAs makes them more stable and less susceptible to degradation [87 – 90].”
Luo, D., Ottesen, E. W., Lee, J. H., & Singh, R. N. (2024) · Scientific Reports · doi:10.1038/s41598-024-60593-7 · Cited by 7
Interaction of noncoding RNAs with hippo signaling pathway in cancer cells and cancer stem cells
Abedimanesh, S., Safaralizadeh, R., Jahanafrooz, Z., Najafi, S., Amini, M. A., Nazarloo, S. S., Mahdavi, S. Z. B., Baradaran, B., Jebelli, A., & Mokhtarzadeh, A. A. (2024) · Non-coding RNA Research · doi:10.1016/j.ncrna.2024.06.006 · Cited by 7
“…from splice sites, their biogenesis depends on the splicing machinery, cis/trans acting factors like SR proteins and heterogeneous nuclear ribonucleoproteins [69,70], which are generated through back splicing. circRNAs are mainly derived from genes consisting of highly active promoters [71].”
BackgroundThe importance of the circRNA/Wnt axis in gliomas: Biological functions and clinical opportunities
Hedayati, N., Mafi, A., Farahani, A., Hashemi, M., Nabavi, N., Alimohammadi, M., Rahimzadeh, P., Taheriazam, A., & Farahani, N. (2024) · Pathology - Research and Practice · doi:10.1016/j.prp.2024.155510 · Cited by 7
Circular RNAs in Hematopoiesis with a Focus on Acute Myeloid Leukemia and Myelodysplastic Syndrome
Merkerová, M. D., Krejčík, Z., Szikszai, K., & Kundrát, D. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21175972 · Cited by 7
“Due to their high stability [14], circRNAs have considerable potential to be used as cancer biomarkers.”
BackgroundInfluentialVariety of Non-Coding RNAs in Eukaryotic Genomes
Nazipova, N. N. (2021) · Mathematical Biology and Bioinformatics · doi:10.17537/2021.16.256 · Cited by 8
Screening of Human Circular RNAs as Biomarkers for Early Onset Detection of Alzheimer’s Disease
Zheng, D., Tahir, R. A., Yan, Y., Zhao, J., Quan, Z., Kang, G., Han, Y., & Qing, H. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.878287 · Cited by 8
Gong, Z., Rong, X., Li, X., Wang, H., Liu, D., He, L., Pan, J., Shen, Q., & Peng, Y. (2022) · The American Journal of Drug and Alcohol Abuse · doi:10.1080/00952990.2022.2073449 · Cited by 7
“5-fold longer than that of their linear transcripts (50).”
BackgroundSun, X.-D., Huan, C., Sun, D., & Lv, G.-Y. (2021) · BioMed Research International · doi:10.1155/2021/8828299 · Cited by 7
“Since circRNAs lack free 3′ or 5′ tails, they are more resistant to exonuclease RNase R-induced degradation and confer longer half-lives than that of linear mRNAs [2, 38, 39].”
BackgroundFission Impossible: Stabilized miRNA-Based Analogs in Neurodegenerative Disease
Lukiw, W. J. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.875957 · Cited by 7
“Stabilized circRNAs may have high therapeutic value in acting as long-lived “sponges” for the inactivation or down-regulation of overly expressed miRNAs in pathological conditions such as AD (Enuka et al., 2016; Mumtaz et al., 2020; Li et al., 2021; Su et al., 2022).”
BackgroundZhang, J., Zeng, L., Wu, Z., Fu, L., Xiao, Z., Zhao, W., Deng, F., Wang, S., Liao, Y., Wang, R., et al. (2023) · Microbial Pathogenesis · doi:10.1016/j.micpath.2023.106003 · Cited by 6
He, J., Dai, Y. E., Liu, J., Lin, H., Gao, F., Chen, Z., & Wu, Y. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2024.1383186 · Cited by 6
Exosomal noncoding RNAs: decoding their role in thyroid cancer progression
Sun, W., Jiang, C., Liu, Q., Wang, N., Huang, R., Jiang, G., & Yang, Y. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1337226 · Cited by 7
Efficient circular RNA synthesis through Gap-DNA splint-mediated ligation
Kim, H., Kim, D., Moon, S., & Lee, J. B. (2024) · Nanoscale · doi:10.1039/d4nr01770f · Cited by 6
Antigen Delivery Platforms for Next-Generation Coronavirus Vaccines
Chentoufi, A. A., Ulmer, J. B., & BenMohamed, L. (2024) · Vaccines · doi:10.3390/vaccines13010030 · Cited by 7
Camandona, A., Gagliardi, A., Licheri, N., Tarallo, S., Francescato, G., Budínská, E., Čarnogurská, M., Zwinsova, B., Martinoglio, B., Franchitti, L., et al. (2025) · Biomarker Research · doi:10.1186/s40364-025-00744-8 · Cited by 6
“CircRNAs are stable molecules that persist in the cytoplasm for several hours, and cells generally produce tightly controlled copies of them [21].”
Backsplicing of the HIV-1 transcript generates multiple circRNAs to promote viral replication
Mauer, C., Paz, S., & Caputi, M. (2025) · npj Viruses · doi:10.1038/s44298-025-00105-0 · Cited by 6
“The lack of 5 ’ and 3 ’ termini make circRNAs highly resistant to degradation by exonucleases resulting in their hyperstability and extremely long half-life 2 .”
Zhang, G., Tu, J., Zhang, Y., He, J., Peng, G., Fan, Q., Zhang, Y., Zhang, M., Tan, H., Xu, Y., et al. (2025) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2025.102620 · Cited by 6
“72,73 In summary, our study demonstrated that nanoparticle delivery of mRNA encoding VEGF-B effectively suppresses tumor growth by eliciting T cell-mediated responses across multiple tumor models while exhibiting minimal toxicity.”
Regulation of partial endothelial-to-mesenchymal transition by circATXN1 in ischemic diseases
Li, Y., Zheng, Z., Li, Y., Fan, S., Kong, L., Fu, W., Li, Z., Zhang, J., Li, S., Liu, Z., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-61596-2 · Cited by 6
“This allows them to withstand RNA exonucleolytic digestion 19 .”
Jenks, K. R., Cai, Y., Nayan, M. E., Tsimring, K., Li, K., Zepeda, J. C., Heller, G. R., Delepine, C., Shih, J., Yuan, S., et al. (2025) · iScience · doi:10.1016/j.isci.2025.113421 · Cited by 7
Capirossi, G., Brasini, S., Tremoli, E., Binatti, A., & Roncarati, R. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26199725 · Cited by 6
“Many circRNAs are typically generated through the back-splicing of exons flanked by adjacent long introns in genes with highly active promoters [18–20].”
State‐of‐the‐Art Strategies for Circular RNA in Cancers: Opportunity and Challenge
Ding, Z., Luo, Z., Zhang, L., Zhang, S., Zhang, R., Qiu, Z., & Huang, C. (2026) · MedComm · doi:10.1002/mco2.70608 · Cited by 6
“Quantitative studies in mammary gland cells have revealed a median circRNA half-life of 18.8 to 23.7 h, in stark contrast to the 4.0–7.4-h half-life observed for their homologous linear RNAs [ 64 ].”
InfluentialIRES–cargo interplay structurally modulates circular RNA translation
Huang, Y., Chen, Y.-Q., Lou, S., Gao, X., Liu, Y.-X., Zhang, Y., Nan, F., Chen, L., & Yang, L. C. (2026) · Cell Research · doi:10.1038/s41422-026-01233-9 · Cited by 8
Tang, S., Cai, L., Wang, Z., Pan, D., Wang, Q., Shen, Y., Zhou, Y. L., & Chen, Q. (2023) · Cancer Innovation · doi:10.1002/cai2.50 · Cited by 6
“Most critically, circRNAs are exceptionally stable and less susceptible to RNA exonuclease cleavage compared with linear mRNAs due to the circular structure [19, 60, 61].”
BackgroundRegulatory effect of Epigallocatechin-3-O-gallate on circular RNA expression in mouse liver
Yoshitomi, R., Kumazoe, M., Lee, K., Marugame, Y., Fujimura, Y., & Tachibana, H. (2023) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2023.109506 · Cited by 6
Wei, Z., Li, H., Lv, S., & Yang, J. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1301545 · Cited by 9
“Compared to mRNA, miRNA, or lncRNA, circRNAs exhibit higher stability in the cytoplasm as therapeutic targets (111, 112).”
BackgroundCancer fusion transcripts with human non-coding RNAs
Mohammad, T., Zolotovskaia, M., Suntsova, M., & Buzdin, A. A. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1415801 · Cited by 7
“CircRNAs were shown to be relatively stable and having a half-life in general longer than that of their linear counterparts by at least 2.5 times (181), Furthermore, circRNAs were abundant in serum exosomes in colorectal cancer (174, 182), thus they potentially can be detected in minimally invasive…”
BackgroundInfluentialRNA-lipid nanoparticle therapeutics for women’s health
Nomani, A., Saraswat, A. L., Zhang, Y., Parenky, A. C., Kuo, C.-T. J., Brown, H., Hartford, S. A., Rayaprolu, B. M., Bhalla, A. S. B., & Shameem, M. (2025) · Frontiers in Nanotechnology · doi:10.3389/fnano.2025.1475969 · Cited by 7
The molecular axis hnRNPU/circKCNK2/EDC4/IL-11 aggravates osteolytic bone metastasis of RCC
Wang, Y., Zhao, D., Lu, J., Hou, N., Wu, Q., Zhou, S., Xu, J., Xue, W., Cui, W., Zheng, J., et al. (2025) · Oncogene · doi:10.1038/s41388-025-03476-z · Cited by 6
Circular RNA circRara promote the innate immune responses in miiuy croaker, Miichthys miiuy
Xin, S., Lv, X., Zheng, W. W., Wang, L., Xu, T., & Sun, Y. (2022) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2022.08.026 · Cited by 6
Smoniewski, C. M., Borujeni, P. M., Petersen, A., Hampton, M. E., Salavati, R., & Zimmer, S. L. (2023) · Scientific Reports · doi:10.1038/s41598-023-34255-z · Cited by 6
Wang, Y., Chen, X., & Yang, Y. (2023) · Clinical & Translational Oncology · doi:10.1007/s12094-023-03285-4 · Cited by 7
“CircRNA occurrence relies on the spliceosome mechanism, and although such splicing is less efficient than conventional linear splicing, it is exceptionally stable because circRNA is formed in a circular structure, lacks a 5' cap and 3' tail and is not easily degraded by RNase [59].”
The role of circular RNA in preeclampsia: From pathophysiological mechanism to clinical application
Zhou, W., Li, X., Li, X., Liu, Y., Song, W., & Yang, Q. (2024) · Life Sciences · doi:10.1016/j.lfs.2023.122407 · Cited by 6
Circular RNAs: Biogenesis, Functions, and Role in Myocardial Hypertrophy
Baulina, N., Сергеевич, К. И., Сергеевна, Ч. О., & Favorova, O. O. (2024) · Biochemistry (Moscow) · doi:10.1134/s0006297924140013 · Cited by 7
Endogenous miRNA sponges mediate the generation of oscillatory dynamics for a non-coding RNA network
Dhawan, A., Harris, A. L., Buffa, F. M., & Scott, J. G. (2019) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2018.10.055 · Cited by 6
Plasma Circular RNA (0054633) Expression as a Biomarker for Prediabetes and Type 2 diabetes mellitus
El-Hefnway, S. M., Al-sheikh, N. M., Kasem, H. E., & El-esrigy, F. (2018) · Bulletin of Egyptian Society for Physiological Sciences · doi:10.21608/besps.2018.8113 · Cited by 6
Zhuang, M., Zhao, J., Wu, J., Fu, S., Han, P., & Song, X. (2021) · BMC Medical Genomics · doi:10.1186/s12920-021-01132-5 · Cited by 6
“In some cases, circRNAs can be relatively long-lived and weakly expressed [9].”
BackgroundLi, H., Zhao, Y., Shen, Q., & Li, H. (2022) · Acta Biochimica et Biophysica Sinica · doi:10.3724/abbs.2022101 · Cited by 6
“For example, many RNA binding proteins [13] like ADAR1, DHX9, FUS and QKI can bind to the complementary intronic elements flanking circRNAs and modulate the biogenesis of circRNAs.”
InfluentialBuilding integrative functional maps of gene regulation
Xu, J., Pratt, H., Moore, J. E., Gerstein, M., & Weng, Z. (2022) · Human Molecular Genetics · doi:10.1093/hmg/ddac195 · Cited by 6
Circular RNAs: Insights into Clinical and Therapeutic Approaches for Various Cancers
Akram, F., Haq, I. U., Nasir, N., & Shah, F. I. (2023) · Current Protein and Peptide Science · doi:10.2174/1389203724666230111113715 · Cited by 6
Circular RNAs and their role in renal cell carcinoma: a current perspective
Liu, Z., & Li, M. (2021) · Cancer Cell International · doi:10.1186/s12935-021-02181-7 · Cited by 6
Wang, J., Wang, C., Fu, L., Wang, Q., Fu, G., Lu, C., Jin, F., Cong, B., & Li, S. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.11.10.376418 · Cited by 6
Circular RNA CDR1as/ciRS-7– a novel biomarker in solid tumors
Zhang, Y., Xiong, C., Jiang, Z., Wang, X., Ji, J., Pan, Y., Yu, T., Wang, Z.-H., Zhu, L., Yue, Y., et al. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1468363 · Cited by 5
Jia, G.-D., Xie, S., Li, X., Li, L., Jin, J., Liu, L., Sun, X.-S., Liu, S.-L., Chen, Q.-Y., Tang, L., et al. (2025) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-025-03468-7 · Cited by 5
“Although their efficiency is lower than that of linear splicing, circRNAs are highly stable once they form and continuously accumulate in cells [7].”
Metadata
- Authors
- Enuka, Y., Lauriola, M., Feldman, M. E., Sas-Chen, A., Ulitsky, I., & Yarden, Y.
- Affiliations
- Weizmann Institute of Science (IL)
- Corresponding author
- Yarden, Yosef
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-12-10
- Volume
- 44
- Issue
- 3
- Pages
- 1370-1383
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC4756822
- OpenAlex
- W2285247593
- Cited by
- 757
- References
- 64
- Citations by year
- 2026: 66 · 2025: 91 · 2024: 100 · 2023: 105 · 2022: 93 · 2021: 107 · 2020: 68 · 2019: 57 · 2018: 33 · 2017: 26 · 2016: 9
- FWCI
- 9.85
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, cc-by-nc)
- HighWire Press Open Archive (submittedVersion)
- 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, epidermal growth factor, mammary epithelial cells, RNA stability, non-coding RNA, microRNA, cell migration, growth factor signaling
- MeSH terms
- RNA, Circular, Breast, Cell Line, Epidermal Growth Factor, Epithelial Cells, Humans, RNA, RNA, Messenger, Gene Expression, Transforming Growth Factor alpha, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, RNA Stability, MicroRNAs, Heparin-binding EGF-like Growth Factor
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