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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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Role of Circular RNAs in Pulmonary Fibrosis
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Circular RNAs in inflammatory bowel disease
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“The expression levels of many circRNAs are very low and many circRNAs have few sites for miRNA binding (78, 87), therefore, these circRNAs may not function as miRNA sponges.”
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Lin, W., Yang, Y., Wang, W., & Xu, R. (2022) · Annals of the Academy of Medicine Singapore · doi:10.47102/annals-acadmedsg.2021405 · Cited by 20
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Qi, L., Sun, B., Yang, B., & Lu, S. (2021) · Cancer Biotherapy and Radiopharmaceuticals · doi:10.1089/cbr.2020.4381 · Cited by 19
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Kirio, K., Patop, I. L., Anduaga, A. M., Harris, J. M., Pamudurti, N. R., Su, T. N., Martel, C., & Kadener, S. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115485 · Cited by 22
Predicting CircRNA-Disease Associations Based on Improved Weighted Biased Meta-Structure
Lei, X., Bian, C., & Pan, Y. F. (2021) · Journal of Computer Science and Technology · doi:10.1007/s11390-021-0798-x · Cited by 18
So, B. Y. F., Yap, D. Y. H., & Chan, T. M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23158509 · Cited by 18
“4 h for their linear counterparts [23].”
The Emerging Roles and Clinical Potential of circSMARCA5 in Cancer
Xue, C., Wei, J., Li, M., Chen, S., Zheng, L., Zhan, Y., Duan, Y., Deng, H., Xiong, W., Li, G., et al. (2022) · Cells · doi:10.3390/cells11193074 · Cited by 18
The function and clinical implication of circular RNAs in lung cancer
Ren, W., Yuan, Y., Peng, J., Mutti, L., & Jiang, X. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.862602 · Cited by 18
“Therefore, circRNAs have much higher stability than their cognate linear transcripts (85).”
BackgroundLiu, Y., He, W., Li, X., Lu, X., Wu, C., Gao, Y. J., Fan, D., Dong, C., & Zhao, H. (2025) · Cell Communication and Signaling · doi:10.1186/s12964-025-02321-w · Cited by 19
“Meanwhile, studies have shown that circRNA is more stable than their linear mRNA counterparts, with circRNA exhibiting a median half-life in mammalian cells that is at least longer than that of linear mRNA [23, 25, 26].”
Perspectives on Circular RNAs as Prostate Cancer Biomarkers
Fang, J., Qi, J., Dong, X., & Luo, J. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.594992 · Cited by 17
Peripheral blood hsa-circRNA5333-4: A novel biomarker for myasthenia gravis
Lv, J., Ren, L., Han, S., Zhang, J., Zhao, X., Zhang, Y., Hua, F., Zhang, L., Yang, H., Wang, S., et al. (2021) · Clinical Immunology · doi:10.1016/j.clim.2021.108676 · Cited by 17
Evaluation of methods to detect circular RNAs from single-end RNA-sequencing data
Nguyen, M. H., Nguyen, H.-N., & Vu, T. N. (2022) · BMC Genomics · doi:10.1186/s12864-022-08329-7 · Cited by 18
“This creates some distinctive features in circRNA, for instance, it degrades the effect of exonuclease digestion, thus preserving circular RNAs longer in the cell [2].”
BackgroundFunction and Clinical Significance of Circular RNAs in Thyroid Cancer
Yao, X., & Zhang, Q. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.925389 · Cited by 18
Localised Cdr1as activity is required for fear extinction memory
Zajaczkowski, E. L., Zhao, Q., Liau, W., Gong, H., Madugalle, S. U., Periyakaruppiah, A., Leighton, L. J., Musgrove, M. R. B., Ren, H., Davies, J., et al. (2023) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2023.107777 · Cited by 15
Kim, Y., Kim, D.-H., An, D., Lim, Y., Seo, Y., Kim, H. K., & Kang, H.-Y. (2023) · Animal Cells and Systems · doi:10.1080/19768354.2023.2265165 · Cited by 17
“Single-stranded circRNA was fi rst discovered in viroids in 1976 (Sanger et al. 1976) and then later in eukaryotes in 1979 (Hsu and Coca-Prados 1979). cir-cRNAs have higher stability than messenger RNA (mRNA) due to a lack of free 5 ′ - and 3 ′ -ends (Enuka et al. 2016).”
BackgroundCircular RNAs in non-alcoholic fatty liver disease: Functions and clinical significance
Zeng, Q., Liu, C., Ampuero, J., Wu, D., Jiang, W., Zhou, L., Li, H., Bai, L., Romero‐Gómez, M., & Tang, H. (2023) · RNA Biology · doi:10.1080/15476286.2023.2290769 · Cited by 18
“The median half-life of circRNAs (18.8–23.7 h) was reportedly at least 2.5 times longer than their cognate linear RNAs (4.0–7.4 h) [36].”
InfluentialRole of circular RNAs in cardiovascular diseases
Gong, X., Wu, G., & Zeng, C. (2019) · Experimental Biology and Medicine · doi:10.1177/1535370218822988 · Cited by 17
“Moreover, they are generally more conserved across species and more abundant in expression, indicating a functional importance in life.(19) Since the first well-studied circRNA, ciRS-7 (CDR1as) came to show its participation in brain development, more studies on functional circRNAs are accumulating.”
BackgroundGhasemi, H., Sabati, Z., Ghaedi, H., Salehi, Z., & Alipoor, B. (2019) · Molecular Biology Reports · doi:10.1007/s11033-019-04937-x · Cited by 16
Nicolet, B. P., Jansen, S. B. G., Heideveld, E., Ouwehand, W. H., van den Akker, E., Lindern, M. V., & Wolkers, M. C. (2021) · RNA · doi:10.1261/rna.078754.121 · Cited by 17
“194 RNA (2022) 28:194–209; Published by Cold Spring Harbor Laboratory Press for the RNA Society lack the 3′ polyadenylation tail, which renders them more stable than linear RNA (Enuka et al. 2016).”
BackgroundHu, Z., Chen, J., Wang, M., Weng, W., Chen, Y., & Pan, Y. (2022) · Molecular Biology Reports · doi:10.1007/s11033-022-07666-w · Cited by 16
The role of non-coding RNAs in muscle aging: regulatory mechanisms and therapeutic potential
Shin, Y. J., Kwon, K., Suh, Y., & Lee, K. (2024) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2023.1308274 · Cited by 16
“These circular structures make circRNAs highly stable and resistant to degradation by cellular machinery, contributing to their longevity within cells (Enuka et al., 2016).”
BackgroundCircular mRNA Vaccine against SARS-COV-2 Variants Enabled by Degradable Lipid Nanoparticles
Huang, K., Li, N., Li, Y., Zhu, J., Fan, Q., Yang, J., Gao, Y., Liu, Y., Gao, S., Zhao, P., et al. (2025) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.4c20770 · Cited by 32
Guo, Y., Huang, Q., Yu, H., Zhou, Y., Chen, H., Xu, C., Wu, C., Tao, L., & Zhou, L. (2025) · MedComm · doi:10.1002/mco2.70079 · Cited by 16
Transfer- or ‘transmission’-RNA fragments? The roles of tsRNAs in the reproductive system
Li, H., Tan, X., Zhang, S., Yao, J., & Li, H.-G. (2021) · Molecular Human Reproduction · doi:10.1093/molehr/gaab026 · Cited by 16
Nanobiotechnology-Enabled mRNA Stabilization
Xian, H., Zhang, Y., Yu, C., & Wang, Y. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15020620 · Cited by 19
“In addition, removal of the 5′ and 3′ ends of mRNA that are necessary for exoribonuclease-mediated degradation forms circular RNA (circRNA), prolonging its half-life compared to linear RNA [48].”
BackgroundThe potential roles of circular RNAs in osteonecrosis of the femoral head (Review)
Zhao, J. B., Mu, L., Wang, Z., Fang, X., He, X., Zhang, X., & Xu, X. (2019) · Molecular Medicine Reports · doi:10.3892/mmr.2019.10866 · Cited by 16
Gao, A.-M., Yuan, C., Hu, A., & Liu, X. (2020) · Cellular Signalling · doi:10.1016/j.cellsig.2020.109622 · Cited by 16
Tian, M., Cao, Z., & Pang, H. (2021) · Molecules · doi:10.3390/molecules26041155 · Cited by 16
“Although the average half-life of a circular RNA can reach 50 h, many factors, such as the length of the amplified products, primer specificity, and endogenous controls, can affect the actual detection level [37,107,127].”
BackgroundDelivery of Circular mRNA via Degradable Lipid Nanoparticles against SARS-CoV-2 Delta VariantPreprint
Huang, K., Li, N., Li, Y., Zhu, J., Fan, Q., Yang, J., Gao, Y., Liu, Y., Hou, Q., Gao, S., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.05.12.491597 · Cited by 16
Advances in mRNA vaccine therapy for breast cancer research
Li, J., Jiang, R., Wang, J., & Wang, X. (2025) · Discover Oncology · doi:10.1007/s12672-025-02542-y · Cited by 16
“CircRNAs lack the terminal motifs required for degradation by exonucleases, rendering them more stable than linear mRNAs [75, 76].”
Emerging roles of circular RNAs in retinal diseases
Zhang, S., Hanineva, A., Park, K., Wang, J., DeAngelis, M. M., & Farkas, M. H. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.335691 · Cited by 15
“Due to the lack of 5′ and 3′ ends, circRNAs are resistant to exonuclease-mediated degradation and are found abundantly expressed throughout the genome (Enuka et al., 2016).”
BackgroundÖzdemir, S., & Arslan, H. (2022) · Chemosphere · doi:10.1016/j.chemosphere.2022.134330 · Cited by 11
Circular RNAs in hepatocellular carcinoma: Recent advances
Niu, Z.-S., & Wang, W. (2022) · World Journal of Gastrointestinal Oncology · doi:10.4251/wjgo.v14.i6.1067 · Cited by 15
Roles of circRNAs in hematological malignancies
Deng, F., Zhang, C., Lu, T., Liao, E. J., Huang, H., & Wei, S. (2022) · Biomarker Research · doi:10.1186/s40364-022-00392-2 · Cited by 15
“RNA sequencing The sequence of circRNA was analyzed by highthroughput sequencing Studying genome-wide differences of circRNAs [19, 52, 97, 98]”
BackgroundMethodCircular RNA regulation and function in drug seeking phenotypes
Daws, S. E., & Gillespie, A. (2023) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2023.103841 · Cited by 15
Circular RNA as a Novel Regulator and Promising Biomarker in Polycystic Ovary Syndrome
Jing, T., Wu, Y., Wan, A., Ge, C., Chen, Z., & Du, Y. (2023) · Biomolecules · doi:10.3390/biom13071101 · Cited by 15
“Firstly, circRNAs have high stability compared to linear RNAs [7], owing to their covalently closed loop structure that resists degradation by exonuclease RNase R [107].”
BackgroundKim, T., Kim, Y. G., Jung, W. S., Jang, S., Ko, H., Park, C. H., Byun, J., & Kim, D. (2023) · Biomolecules · doi:10.3390/biom13111646 · Cited by 15
“Unlike linear RNA, circRNAs are more protected from the degradation by exonucleases This circular structure is generated by a specialized process called backsplicing [170]. and consequently have an extended half-life [171].”
BackgroundEmerging Roles of Circular RNA in Macrophage Activation and Inflammatory Lung Responses
Son, C. J., Carnino, J. M., Lee, H., & Jin, Y. (2024) · Cells · doi:10.3390/cells13171407 · Cited by 17
“…the MVBs and, subsequently, transported to autophagosomes and lysosomes, and/or merged As mentioned above, due to the circular form and the absence of a free 5′ cap and 3′ poly A ends, circRNAs are more resistant to exonucleases [5,19], resulting in the accumulation of circRNAs intracellularly.”
BackgroundPu, J., Yan, X., & Zhang, H. (2024) · Journal of Advanced Research · doi:10.1016/j.jare.2024.11.032 · Cited by 15
“Enuka et al. [33] determined the half-life of 61 circRNAs and found that they are generally less abundant than their corresponding linear RNAs.”
Circular RNA-Centered Regulatory Networks in the Physiopathology of Cardiovascular Diseases
Gabriel, A. F., Costa, M. C., & Enguita, F. J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21020456 · Cited by 15
“Once the circular structure is formed, circRNAs become highly resistant to nuclease action, such as RNAse R [15,16], which means that their half-life is usually higher than other linear RNA molecules [17].”
BackgroundWen, G., & Gu, W. (2022) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.17525 · Cited by 14
Özdemir, S., Aksungur, N., Altundaş, N., Kara, S., Korkut, E., Özkaraca, M., Mendĭl, A. S., & Öztürk, G. (2022) · Gene · doi:10.1016/j.gene.2021.146161 · Cited by 14
Wang, Z., Yu, R., Chen, X., Bao, H., Cao, R., Li, A., Ou, Q., Tu, H., Zhou, Q. H., Wu, X., et al. (2022) · Journal of Translational Medicine · doi:10.1186/s12967-022-03274-1 · Cited by 14
“The percentage of circRNAs was the same as previously found in brain tissue [44] and ranged from 47 to 81% of the total CSF-circRNAs in each patient (Additional file 5: Table S6).”
BackgroundResultSynthetic RNA Therapeutics in Cancer
Han, Y., Shin, S.-H., Lim, C. G., Heo, Y. H., Choi, I. Y., & Kim, H. H. (2023) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.123.001587 · Cited by 14
“Unlike linear RNAs which are susceptible to degradation by exonucleases and hydrolysis, circRNA is covalently closed and more resistant to degradation by enzymes displaying extended half-lives relative to linear RNA (Enuka et al., 2016; X Liu et al., 2022).”
BackgroundStudy of Circular RNA Expression by Nonradioactive Northern Blot Procedure
D’Ambra, E., & Morlando, M. (2021) · Methods in molecular biology · doi:10.1007/978-1-0716-1581-2_23 · Cited by 15
Interplay between circular RNA, microRNA, and human diseases
Kour, B., Gupta, S., Singh, R., Sophiarani, Y., & Paul, P. (2022) · Molecular Genetics and Genomics · doi:10.1007/s00438-022-01856-8 · Cited by 14
Feng, H., Deng, Z., Peng, W., Wei, X., Liu, J., & Wang, T. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04132-4 · Cited by 14
New Insight of Circular RNAs' Roles in Central Nervous System Post-Traumatic Injury
Xu, L., Ye, X., Zhong, J., Chen, Y., & Wang, L. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.644239 · Cited by 14
“Although most functions remain unknown, circRNAs have been shown to function as templates for viroid and viral replication, as intermediates in RNA processing reactions, as regulators of transcription in cis, as snoRNAs, and as miRNA sponges (Lasda and Parker, 2014; Enuka et al., 2016).”
BackgroundCasmil, I. C., Friesen, J. J., Bathula, N. V., Strumpel, A., Ho, C.-H., Guez, I., Kong, K. Y. S., Varley, A., Miyake-Stoner, S. J., Aliahmad, P., et al. (2025) · Advanced Science · doi:10.1002/advs.202508907 · Cited by 17
Role of circular RNA in hematological malignancies (Review)
Mei, M., Wang, Y., Li, Z., & Zhang, M. (2019) · Oncology Letters · doi:10.3892/ol.2019.10836 · Cited by 13
“Due to their natural resistance to exonucleases, circRNAs appear to be extremely stable transcripts with half‐lives of >24‐48 h (25).”
BackgroundZhang, X., & Zheng, X. (2022) · Reproductive Biology · doi:10.1016/j.repbio.2022.100648 · Cited by 13
Circular RNAs in Diabetic Nephropathy: Updates and Perspectives
Liu, M., & Zhao, J. (2022) · Aging and Disease · doi:10.14336/ad.2022.0203 · Cited by 13
Exploring circular MET RNA as a potential biomarker in tumors exhibiting high MET activity
Bersani, F., Picca, F., Morena, D., Righi, L., Napoli, F., Russo, M., Oddo, D., Rospo, G., Negrino, C., Castella, B., et al. (2023) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-023-02690-5 · Cited by 13
“On the other hand, circularization confers intrinsic resistance to exonuclease [2], resulting in higher stability and prolonged half-life compared to the cognate linear RNA [15, 18].”
BackgroundCircular RNAs: An emerging precise weapon for diabetic nephropathy diagnosis and therapy
Shu, H., Zhang, Z., Liu, J., Chen, P., Yang, C., Wu, Y., Wu, D., Cao, Y., Chu, Y., & Li, L. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115818 · Cited by 13
Noncanonical circRNA biogenesis driven by alpha and gamma herpesviruses
Dremel, S. E., Kopardé, V. N., Arbuckle, J. H., Hogan, C. H., Kristie, T. M., Krug, L. T., Conrad, N. K., & Ziegelbauer, J. M. (2025) · The EMBO Journal · doi:10.1038/s44318-025-00398-0 · Cited by 13
“CircRNAs are currently being investigated as a mechanism for mRNA-vaccine delivery as they have low immunogenicity, long half-lives, and the potential for cap-independent translation (Enuka et al, 2016; Pamudurti et al, 2017; Qu et al, 2022).”
Interactions Among Regulatory Non-coding RNAs Involved in Cardiovascular Diseases
Gabriel, A. F., Costa, M. C., & Enguita, F. J. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-981-15-1671-9_4 · Cited by 13
Shi, Y., Tian, Y., Sun, X., Qiu, Y., & Zhao, Y. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.889583 · Cited by 14
“To investigate the interactions between circOMA1 and its potential targeted miRNAs, the expressions of miR-654-3p, miR330-3p, and miR-1294 were evaluated in transfected cells (Figure 3B).”
BackgroundInfluentialLarge-scale manufacturing of base-edited chimeric antigen receptor T cells
Woodruff, R., Parekh, F., Lamb, K., Mekkaoui, L., Allen, C. G., Smetanova, K., Huang, J. L., Williams, A., Toledo, G. S., Lilova, K., et al. (2023) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2023.101123 · Cited by 14
“As previous studies have reported the improved half-life and translational capacity of circRNAs, 46,65 – 67 we monitored the stability of BE4max-encoding linear and circular RNA in T cells.”
MethodRaimondo, D. D., Pirera, E., Rizzo, G., Simonetta, I., Musiari, G., & Tuttolomondo, A. (2022) · Diagnostics · doi:10.3390/diagnostics12061355 · Cited by 12
“[51] estimate that circRNAs have a half-life of 18.”
BackgroundDiscovery of novel microRNA mimic repressors of ribosome biogenesis
Bryant, C. J., McCool, M. A., Rosado-González, G. T., Abriola, L., Surovtseva, Y. V., & Baserga, S. J. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad1235 · Cited by 12
“BioProject accession GEO samples used Reference PRJNA290557 GSM1829628 (60) PRJNA384982 GSM2593351, GSM2593352, GSM2593353 (61) PRJNA530983 GSM3711368, GSM3711369 N/A PRJNA647393 GSM4667014, GSM4667015, GSM4667016 (62)”
Expanding roles of circRNAs in cardiovascular diseases
Liu, X., Yao, X., & Chen, L. (2024) · Non-coding RNA Research · doi:10.1016/j.ncrna.2024.02.001 · Cited by 12
“Abundant circRNAs tend to be derived from genes with highly active promoters [25,26].”
BackgroundAssembling the RNA therapeutics toolbox
Teng, M., Xia, Z. J., Lo, N., Daud, K., & He, H. H. (2024) · Medical Review · doi:10.1515/mr-2023-0062 · Cited by 12
Chen, X., Xu, H., Lin, Y., & Zhu, B. (2024) · Forensic Science International · doi:10.1016/j.forsciint.2024.112148 · Cited by 13
Imaging and quantification of human and viral circular RNAs
Jaijyan, D. K., Yang, S., Ramasamy, S., Gu, A., Zeng, M., Subbian, S., Tyagi, S., & Zhu, H. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae583 · Cited by 12
Emerging Roles of ncRNAs in Type 2 Diabetes Mellitus: From Mechanisms to Drug Discovery
Yang, Y., & Cheng, H. (2024) · Biomolecules · doi:10.3390/biom14111364 · Cited by 11
Li, W., Xue, X., Li, X., Wu, X., Zhou, P., Xia, Y., Zhang, J., Zhang, M., & Zhu, F. (2024) · Cell & Bioscience · doi:10.1186/s13578-024-01318-1 · Cited by 13
“CircRNAs, characterized by their circular structure and lack of free ends, exhibit greater stability compared to linear RNAs, as they are resistant to degradation by exonucleases [80].”
Circular RNAs increase during vascular cell differentiation and are biomarkers for vascular disease
Northoff, B. H., Herbst, A., Wenk, C., Weindl, L., Gäbel, G., Brezski, A., Zarnack, K., Küpper, A., Dimmeler, S., Moretti, A., et al. (2025) · Cardiovascular Research · doi:10.1093/cvr/cvaf013 · Cited by 12
“52,53 Therefore, over time, circRNAs should passively accumulate more than linear RNA in non-dividing cells.”
Tandem DNAzyme for double digestion: a new tool for circRNA suppression
Ding, J., Zhou, W., Li, X., Sun, M., Ding, J., & Zhu, Q. (2018) · Biological Chemistry · doi:10.1515/hsz-2018-0232 · Cited by 12
Research Progress of Circular RNA in Gastrointestinal Tumors
Fang, N., Ding, G., Ding, H., Li, J., Liu, C., Lv, L., & Shi, Y. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.665246 · Cited by 12
Chen, Y., Li, X., Meng, S., Huang, S., Chang, S., & Shi, J. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.839233 · Cited by 12
“The structure of circRNA makes them more stable and has a longer half-life, so it is considered to be a more ideal marker (Enuka et al., 2016).”
BackgroundNokkeaw, A., Thamjamrassri, P., Tangkijvanich, P., & Ariyachet, C. (2023) · Cells · doi:10.3390/cells12030378 · Cited by 13
“Back-splicing is naturally unfavorable [45]; consequently, most circRNAs are less abundant than their linear mRNA isoforms [46].”
BackgroundYuechen, Z., Xi, S., Zhouxing, Z., Gu, F., & Hu, W. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1125888 · Cited by 12
Yousuf, S., Malik, W. A., Feng, H., Liu, T., Xie, L., & Miao, X. (2023) · Journal of Ovarian Research · doi:10.1186/s13048-023-01178-2 · Cited by 12
Expression and Secretion of Circular RNAs in the Parasitic Nematode, Ascaris suum
Minkler, S. J., Loghry, H. J., Sondjaja, N. A., & Kimber, M. J. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.884052 · Cited by 11
“Circular RNAs (circRNAs) are a species of long, noncoding RNA that do not contain an open 5′ or 3’ end but instead form a circular structure that is more stable than linear RNA species (Enuka et al., 2016).”
BackgroundCircular RNAs as emerging regulators in COVID-19 pathogenesis and progression
Gao, X., Fang, D., Liang, Y., Deng, X., Chen, N., Min De, Z. E. N. G., & Luo, M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.980231 · Cited by 13
Chen, L., Song, L., Yang, J., Li, T., Ju, R., Sun, C., & Xie, Z. (2025) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2025.102587 · Cited by 12
“8,35,36 A 4.6 × 300 mm column (Sepax Technologies, HPLC-26) with a particle size of 5 μ m was employed for the separation, with elution carried out at a flow rate of 0.3 mL/min in RNase-free TE buffer (10 mM Tris and 1 mM EDTA [pH 6]).”
InfluentialRNA biomarkers for alcohol use disorder
Ferguson, L. B., Mayfield, R. D., & Messing, R. O. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.1032362 · Cited by 12
Circular RNAs: New players involved in the regulation of cognition and cognitive diseases
Yu, X., Liu, H., Chang, N., Fu, W., Guo, Z., & Wang, Y. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1097878 · Cited by 11
CPSF3 Promotes Pre-mRNA Splicing and Prevents CircRNA Cyclization in Hepatocellular Carcinoma
Huang, Y., Dong, J., wang, X., Ji, H., He, Z., Cheng, Z., & Zhu, Q. (2023) · Cancers · doi:10.3390/cancers15164057 · Cited by 11
“Additionally, circRNAs are considered more stable biomarkers and therapeutic targets compared to other RNAs because they lack a 5′-cap and 3′-poly(A) tail, which results in them being resistant to degradation by the exonuclease RNase [13].”
BackgroundCircRNA and Stroke: New Insight of Potential Biomarkers and Therapeutic Targets
Chen, X., Tan, Q., Chen, K.-J., Zheng, D., Deng, H., He, S., Mao, F., Hao, J., Le, W., & Yang, J. (2023) · Neurochemical Research · doi:10.1007/s11064-023-04077-6 · Cited by 11
“As a result, circRNA can accu - mulate in living organisms [ 11 ].”
Interferon induced circRNAs escape herpesvirus host shutoff and suppress lytic infection
Dremel, S. E., Tagawa, T., Kopardé, V. N., Hernandez-Perez, C., Arbuckle, J. H., Kristie, T. M., Krug, L. T., & Ziegelbauer, J. M. (2024) · EMBO Reports · doi:10.1038/s44319-023-00051-z · Cited by 11
“As circRNAs lack ends, they are generally resistant to exoribonucleases with approximately 2.5-fold longer half-lives than their linear counterparts (Enuka et al, 2016; Memczak et al, 2013).”
BackgroundInfluentialDai, T., Qiu, S., Gao, X., Zhao, C., Ge, Z., Yang, Y., Tang, C., & Feng, S. (2024) · Cancer Science · doi:10.1111/cas.16067 · Cited by 11
“29 We confirmed that circWNK1 has a longer half-life and increased resistance to RNase R versus WNK1 mRNA.”
Noncoding RNAs in skeletal development and disorders
Yao, Q., He, T., Liao, J., Liao, R., Wu, X., Lin, L., & Xiao, G. (2024) · Biological Research · doi:10.1186/s40659-024-00497-y · Cited by 11
“Compared to linear RNAs, circRNAs prefer to localize in the cytoplasm [61– 63], have lower expression levels [63–65], and are more stable [66]. circRNAs can also be divided into coding and non-coding circRNAs, like linear RNAs.”
BackgroundSystematic loss-of-function screens identify pathway-specific functional circular RNAs
Liu, L., Neve, M., Perlaza-Jiménez, L., Xi, X., Purcell, J., Hawdon, A., Conn, S. J., Zenker, J., Tamayo, P., Goodall, G. J., et al. (2024) · Nature Cell Biology · doi:10.1038/s41556-024-01467-y · Cited by 10
“Although circRNAs are very stable and are degraded at a slower rate by the RNA degradation machinery 44,45 , a minimal number of circRNAs is likely to be required for mediating a function.”
Back to the Origin: Mechanisms of circRNA-Directed Regulation of Host Genes in Human Disease
Yuan, H.-M., Liao, X., Hu, D., Guan, D., & Tian, M. (2024) · Non-Coding RNA · doi:10.3390/ncrna10050049 · Cited by 11
“Due to the absence of a cap structure in the 5 ′ end and a poly-A tail in the 3 ′ end, circRNAs are not easily degraded by nucleic acid exonucleases, which makes them more stable than mRNAs [2,3].”
BackgroundSong, W., Chen, X., Haiying, W., & Rahimian, N. (2024) · European journal of medical research · doi:10.1186/s40001-024-02230-7 · Cited by 14
Gu, Y., Ci, C., Wang, Y., Su, M., Lv, W., Zhang, M., Chen, C., Liu, H., Zhang, S., Zhang, Y., et al. (2019) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2019.00365 · Cited by 11
“circRNAs are weakly expressed and have a long halflife (Enuka et al., 2016).”
BackgroundInfluentialMultiple novel functions of circular RNAs in diabetes mellitus
Tehrani, S. S., Goodarzi, G., Panahi, G., Maniati, M., & Meshkani, R. (2021) · Archives of Physiology and Biochemistry · doi:10.1080/13813455.2021.1933047 · Cited by 11
“Their stability (24 – 48 h) is much longer than that of linear RNAs (8.5 h) (Harland and Misher 1988, Enuka et al. 2016, Zheng et al. 2016).”
BackgroundInfluentialMolecular and cellular functions of long non-coding RNAs in prostate and breast cancer
Zhu, Y., & Zhu, J. (2022) · Advances in clinical chemistry · doi:10.1016/bs.acc.2021.09.005 · Cited by 13
Circulating Non-coding RNAs and Cardiovascular Diseases
Zhao, C., Lv, Y., Duan, Y., Li, G., & Zhang, Z. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-981-15-1671-9_22 · Cited by 11
Analysis of the Circular Transcriptome in the Synaptosomes of Aged Mice
Curry‐Hyde, A., Ueberham, U., Chen, B. J., Zipfel, I., Mills, J. D., Bochmann, J., Jendrek, R., Takenaka, K., Kirazov, L., Kirazov, E. P., et al. (2020) · Neuroscience · doi:10.1016/j.neuroscience.2020.09.009 · Cited by 11
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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