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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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Items 101–200 of 765
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“5 times longer compared with their linear RNA form.(20) RNase R degradation can accurately select the closed-loop nature of circRNA over their linear forms as they can degrade linear RNA and its poly-A tail.”
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“Recently, circRNAs have been found to be expressed in various cell lines and species, and they are conserved and highly specific to cell type, tissue, or developmental stage.(14,15) Emerging studies have revealed that circRNAs play important roles in the regulation of multiple diseases, especially cancers.”
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Chen, B. J., Mills, J. D., Takenaka, K., Bliim, N., Halliday, G. M., & Janitz, M. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13752 · Cited by 84
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BackgroundInfluentialCircular RNA: functions, applications and prospects
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“CDR1as, circRNA of Sry, circHIPK3, circFOXO3, circ-TTBK2 and circCCDC66) (5–10) were confirmed to play a regulatory role in microRNA sponges suggests that circRNAs function in the cytoplasm, it was observed no significant excess of miRNA seed matches in the detected circRNAs, expecting that only few circRNAs can act a…”
BackgroundHow are circRNAs translated by non-canonical initiation mechanisms?
Diallo, L. H., Tatin, F., David, F., Godet, A.-C., Zamora, A., Prats, A., Garmy-Susini, B. H., & Lacazette, É. (2019) · Biochimie · doi:10.1016/j.biochi.2019.06.015 · Cited by 84
Potential Diagnostic Power of Blood Circular RNA Expression in Active Pulmonary Tuberculosis
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“Due to the remarkable stability of circRNAs (Enuka et al., 2016), several groups have already investigated circRNA expression in easily accessible human body fluids to determine the potential of circRNAs as biomarkers (Alhasan et al.”
BackgroundInfluentialEmerging Role of Circular RNAs in Cancer
Liu, J., Zhang, X., Yan, M., & Li, H. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00663 · Cited by 77
“Multiple studies have reported that circRNAs have longer half-lives than linear transcripts both in vitro and in vivo (39, 40).”
BackgroundMechanisms of circular RNA degradation
Ren, L., Jiang, Q., Mo, L., Tan, L., Dong, Q., Meng, L., Yang, N., & Li, G. (2022) · Communications Biology · doi:10.1038/s42003-022-04262-3 · Cited by 84
Circular RNA HIPK3 promotes glioma progression by binding to miR-124-3p
Hu, D., & Zhang, Y. (2018) · Gene · doi:10.1016/j.gene.2018.11.073 · Cited by 80
mRNA vaccines: the most recent clinical applications of synthetic mRNA
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“Circular RNA is also found endogenously, which is produced by a back-splicing mechanism, and some of them play a role in expressing proteins in humans (Jeck and Sharpless 2014; Chen and Yang 2015; Wang and Wang 2014; Enuka et al. 2015; Legnini et al. 2017).”
BackgroundCircular RNA; a new biomarker for breast cancer: A systematic review
Jahani, S., Nazeri, E., Majidzadeh‐A, K., Jahani, M., & Esmaeili, R. (2020) · Journal of Cellular Physiology · doi:10.1002/jcp.29558 · Cited by 79
“These exons and surrounding introns can be exceptionally longer than the average and can mostly overlap with the protein‐coding genomic areas (Enuka et al., 2016; Jeck et al., 2013; Memczak et al., 2013; Salzman, Gawad, Wang, Lacayo, & Brown, 2012).”
BackgroundCircular RNAs in the human brain are tailored to neuron identity and neuropsychiatric disease
Dong, X., Bai, Y., Liao, Z., Gritsch, D., Liu, X., Wang, T., Borges-Monroy, R., Ehrlich, A., Serrano, G. E., Feany, M. Β., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-40348-0 · Cited by 83
“The stable circular transcripts have half-lives (18.8 to 23.7 h) that are at least 2.5 times longer than the median half-life of their linear counterparts (4.0 to 7.4 h) 13,14 and these properties may be important for their accumulation in terminally differentiated neurons.”
InfluentialEmerging Role of Circular RNAs as Potential Biomarkers for the Diagnosis of Human Diseases
Ojha, R., Nandani, R., Chatterjee, N., & Prajapati, V. K. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-1426-1_12 · Cited by 76
Zhou, M., Yang, Z., Wang, D., Chen, P., & Zhang, Y. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-01849-2 · Cited by 78
Circular RNA: Biosynthesis in vitro
Chen, X., & Lu, Y. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2021.787881 · Cited by 74
“Endogenously produced circRNAs are 2–5 times more stable than linear RNAs (Enuka et al., 2016; Holdt et al., 2018).”
BackgroundmRNA therapeutics: New vaccination and beyond
Wei, H. Y., Zheng, L., & Wang, Z. (2023) · Fundamental Research · doi:10.1016/j.fmre.2023.02.022 · Cited by 77
“Firstly, they have higher cellular stability than the cognate linear mRNAs as reported by multiple groups [61 , 65 , 66] , possibly due to their resistance to degradation by exonuclease in vitro and/or by the resistance to the immune-induced linear RNA decay machinery in vivo [67] .”
BackgroundTherapeutic application of circular RNA aptamers in a mouse model of psoriasis
Guo, S.-K., Liu, C., Xu, Y.-F., Wang, X., Fang, N., Huang, Y., Li, S., Nan, S., Li, L., Kon, E., et al. (2024) · Nature Biotechnology · doi:10.1038/s41587-024-02204-4 · Cited by 79
“The unique circRNAs’ conformation 5,6 , stability 3,4 and immunogenicity 7,8,57 have endowed them with potential for therapeutic advantages.”
New progresses of circular RNA biology: from nuclear export to degradation
Zhou, M., Xiao, M., Li, Z., & Huang, C. (2020) · RNA Biology · doi:10.1080/15476286.2020.1853977 · Cited by 72
Liu, J., Zhang, Y., Liu, C., Jiang, Y., Wang, Z., Guo, Z., & Li, X. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.07.018 · Cited by 77
Behind the scenes: How RNA orchestrates the epigenetic regulation of gene expression
Mangiavacchi, A., Morelli, G., & Orlando, V. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1123975 · Cited by 76
“5 times longer than linear transcripts (Enuka et al., 2016), so stable that they have provocatively been proposed as molecular memory tools that neurons can exploit to keep track of synaptic events (Rybak-Wolf et al.”
BackgroundCircular RNAs in colorectal cancer: Possible roles in regulation of cancer cells
Taborda, M. I., Ramírez, S., & Bernal, G. (2017) · World Journal of Gastrointestinal Oncology · doi:10.4251/wjgo.v9.i2.62 · Cited by 68
Margvelani, G., Maquera, K. A. A., Welden, J. R., Rodgers, D. W., & Stamm, S. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae1167 · Cited by 81
Lei, X., & Fang, Z. (2019) · International Journal of Biological Sciences · doi:10.7150/ijbs.33806 · Cited by 71
“A stable closed loop structure of circRNAs also helps circRNAs own longer half-lives than the usual linear RNAs[21], which can be regarded as a unique property to diagnose some circRNA-related diseases.”
BackgroundCircular RNAs in diabetes mellitus and its complications
Fan, W., Pang, H., Xie, Z., Huang, G., & Zhou, Z. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.885650 · Cited by 84
Circular RNAs: A Novel Player in Development and Disease of the Central Nervous System
Xie, L., Mao, M., Xiong, K., & Jiang, B. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00354 · Cited by 70
“CircRNAs as Potential Biomarkers in CNS Disorders Due to lack of 3 termini, circRNAs are generally endowed with a strong resistance to exonuclease RNase R, thus being more stable than linear RNAs (Memczak et al., 2013; Enuka et al., 2016).”
BackgroundCircular RNA s: Methodological challenges and perspectives in cardiovascular diseases
Carrara, M., Fuschi, P., Ivan, C., & Martelli, F. (2018) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13789 · Cited by 68
“5 time longer than their linear counterparts.(6,7) They are also resistant to exonucleases, including RNase R, because of the absence of a free tail to initiate the degradation.”
BackgroundCircular RNA GATAD2A promotes H1N1 replication through inhibiting autophagy
Yu, T., Ding, Y., Zhang, Y., Liu, Y., Li, Y., Lei, J., Zhou, J., Song, S., & Hu, B. (2019) · Veterinary Microbiology · doi:10.1016/j.vetmic.2019.03.012 · Cited by 69
Circular RNAs and their roles in head and neck cancers
Guo, Y., Yang, J., Huang, Q., Hsueh, C., Zheng, J., Wu, C., Chen, H., & Zhou, L. F. (2019) · Molecular Cancer · doi:10.1186/s12943-019-1003-5 · Cited by 70
Feng, Z., Zhang, X., Zhou, J., Li, Q., Chu, L., Di, G., Xu, Z., Chen, Q., Wang, M., Jiang, X., et al. (2023) · Nature Cancer · doi:10.1038/s43018-023-00650-8 · Cited by 70
“Circular RNA (cir-cRNA) is an effective strategy for enhancing mRNA stability, especially for cap-independent mechanisms of IRES IVT-mRNA-initiated pattern translation 35 .”
Chang, X., Zhu, G., Cai, Z., Wang, Y., Lian, R., Tang, X., Ma, C., & Fu, S. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.771552 · Cited by 68
“Because its closed loop structure is difficult to degrade by nucleases, circRNA is more stable than its linear transcript (24).”
BackgroundPrecision RNA base editing with engineered and endogenous effectors
Pfeiffer, L. S., & Stafforst, T. (2023) · Nature Biotechnology · doi:10.1038/s41587-023-01927-0 · Cited by 68
“These must be explored in long-term studies, in particular, for circular gRNA embodi-ments, which are very resistant to degradation compared to their linear analogs and accumulate in cells 152,162 .”
BackgroundAbere, B., Li, J., Zhou, H., Toptan, T., Moore, P. S., & Chang, Y. (2020) · mBio · doi:10.1128/mbio.03027-19 · Cited by 67
“5 times longer than that of their linear counterparts (31, 32, 46, 75).”
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“Endogenous circRNAs lack the 5 and 3 ends due to circularization, so they can escape from the exonucleasemediated degradation, being actively resistant to multiple RNA turnover mechanisms (Enuka et al., 2016; Kaczmarek et al., 2017).”
BackgroundCircular RNAs in Sepsis: Biogenesis, Function, and Clinical Significance
Beltrán-García, J., Osca-Verdegal, R., Nácher-Sendra, E., Pallardó, F. V., & García‐Giménez, J. L. (2020) · Cells · doi:10.3390/cells9061544 · Cited by 66
“5-fold longer than their linear homologs [31].”
BackgroundDirect detection of circRNA in real samples using reverse transcription-rolling circle amplification
Liu, Y., Zhang, X., Liu, M., Xu, F., Zhang, Q., Zhang, Y., Weng, X., Liu, S., Du, Y., & Zhou, X. (2019) · Analytica Chimica Acta · doi:10.1016/j.aca.2019.12.027 · Cited by 65
Circular RNA and Diabetes: Epigenetic Regulator with Diagnostic Role
Abbaszadeh‐Goudarzi, K., Radbakhsh, S., Pourhanifeh, M. H., Khanbabaei, H., Davoodvandi, A., Fathizadeh, H., Sahebkar, A., Shahrzad, M. K., & Mirzaei, H. (2020) · Current Molecular Medicine · doi:10.2174/1566524020666200129142106 · Cited by 64
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Computational approaches for circular RNA analysis
Jakobi, T., & Dieterich, C. (2019) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1528 · Cited by 64
“Due to their circular structure, circRNAs have also been shown to be more stable than linear transcripts (Enuka et al., 2016), making them interesting candidates for biomarkers, especially in cancer research (Li et al., 2015).”
BackgroundOptimization of formulation and atomization of lipid nanoparticles for the inhalation of mRNA
Miao, H., Huang, K., Li, Y., Li, R., Zhou, X., Shi, J., Tong, Z., Sun, Z., & Yu, A. (2023) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2023.123050 · Cited by 66
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“At present, only one study reported that genes with circular RNAs show lower DNA methylation in promoters and gene bodies (Enuka et al. 2016).”
BackgroundCircular RNAs: New layer of complexity evading breast cancer heterogeneity
Dawoud, A., Zakaria, Z. I., Rashwan, H. H., Braoudaki, M., & Youness, R. A. (2022) · Non-coding RNA Research · doi:10.1016/j.ncrna.2022.09.011 · Cited by 61
“…al. potential biomarker for several oncological diseases including BC. CircRNAs are 1) Stable: this is due to the covalently closed loop structure, therefore making it highly resistant to exonuclease RNase R and more stable and have longer half-live in plasma than any other linear lncRNA [130,131].”
BackgroundChemoresistance in pancreatic cancer: Emerging concepts
Gnanamony, M., & Gondi, C. S. (2017) · Oncology Letters · doi:10.3892/ol.2017.5777 · Cited by 61
“CiRS-7 has been shown to suppress miR-7 activity (58). circRNAs are also more stable compared with linear miR, and this phenomenon may be exploited to artificially target oncogenic miRs (60).”
Circular RNAs: The Brain Transcriptome Comes Full Circle
Gokoolparsadh, A., Loy, C. T., Halliday, G. M., & Voineagu, I. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.07.007 · Cited by 61
Breaking the mold with RNA—a “RNAissance” of life science
Jones, C. H., Androsavich, J. R., So, N., Jenkins, M. P., MacCormack, D., Prigodich, A. E., Welch, V., True, J. M., & Dolsten, M. (2024) · npj Genomic Medicine · doi:10.1038/s41525-023-00387-4 · Cited by 70
“Due to their closed-loop structure, circRNAs are inaccessible to exonucleases and resistant to mRNA turnover via CCR4-NOT1-or DCP-dependent decay 49,51 .”
Extracellular Vesicle‐Associated RNA as a Carrier of Epigenetic Information
Liegro, C. M. D., Schiera, G., & Liegro, I. D. (2017) · Genes · doi:10.3390/genes8100240 · Cited by 64
“circRNAs are mainly produced by a particular type of alternative splicing called ‘back-splicing’ [188]; one of their most important properties is their exceptional stability and long half-lives [189], probably due to the fact that 3′- and 5′-ends are closed together and therefore not accessible to exonucleolytic degra…”
Circular RNA expression and function in the brain
Sekar, S., & Liang, W. S. (2019) · Non-coding RNA Research · doi:10.1016/j.ncrna.2019.01.001 · Cited by 64
Methods for analysis of circular RNAs
Pandey, P. R., Munk, R. B., Kundu, G., De, S., Abdelmohsen, K., & Gorospe, M. (2019) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1566 · Cited by 61
“Due to the lack of free ends, circRNAs are substantially more stable than their linear counterparts (Enuka et al., 2016).”
BackgroundMa, J., Du, W. W., Zeng, K., Wu, N., Fang, L., Lyu, J., Yee, A., & Yang, B. B. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.08.002 · Cited by 59
Analysis of the circular RNA transcriptome in endometrial cancer
Chen, B. J., Byrne, F. L., Takenaka, K., Modesitt, S. C., Olzomer, E. M., Mills, J. D., Farrell, R., Hoehn, K. L., & Janitz, M. (2017) · Oncotarget · doi:10.18632/oncotarget.23534 · Cited by 57
The Role of lncRNA in the Development of Tumors, including Breast Cancer
Smolarz, B., Zadrożna-Nowak, A., & Romanowicz, H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22168427 · Cited by 57
“The recently discovered circular RNA (circRNA) is a highly stable molecule with a half-life of approximately 19–24 h [3,11].”
BackgroundNon-coding RNAs and glioblastoma: Insight into their roles in metastasis
Mousavi, S. M., Derakhshan, M., Baharloii, F., Dashti, F., Mirazimi, S. M. A., Mahjoubin‐Tehran, M., Hosseindoost, S., Goleij, P., Rahimian, N., Hamblin, M. R., et al. (2021) · Molecular Therapy — Oncolytics · doi:10.1016/j.omto.2021.12.015 · Cited by 56
“circRNAs are a type of ncRNA that may function as specific sponges of miRNAs.(76,77) A group of circRNAs has been recently shown to have a crucial role in the development of glioma.”
BackgroundNext RNA Therapeutics: The Mine of Non-Coding
Garbo, S., Maione, R., Tripodi, M., & Battistelli, C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23137471 · Cited by 62
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Circular RNA—Is the Circle Perfect?
Caba, L., Florea, L., Gug, C., Dimitriu, D. C., & Gorduza, E. V. (2021) · Biomolecules · doi:10.3390/biom11121755 · Cited by 56
CircRNA as an Achilles heel of cancer: characterization, biomarker and therapeutic modalities
Zhang, J., Luo, Z., Yang, Z. K., Duan, M., Qiu, Z., & Huang, C. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-05562-4 · Cited by 58
“CircRNAs are exceptionally stable molecules with higher stability than linear transcripts [33].”
BackgroundIzuogu, O. G., Alhasan, A. A., Mellough, C., Collin, J., Gallon, R., Hyslop, J., Mastrorosa, F. K., Ehrmann, I. E., Lako, M., Elliott, D. J., et al. (2018) · BMC Genomics · doi:10.1186/s12864-018-4660-7 · Cited by 55
“[32] who found that stimulation of mammary cells by EGF did not affect circRNA abundance.”
BackgroundResultMolecular functions and specific roles of circRNAs in the cardiovascular system
Holdt, L. M., Kohlmaier, A., & Teupser, D. (2018) · Non-coding RNA Research · doi:10.1016/j.ncrna.2018.05.002 · Cited by 55
Ma, Y., Wang, T., Zhang, X., Wang, P., & Long, F. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-06698-3 · Cited by 59
“The longer half-lives of circRNAs (18.8 – 23.7 h) compared to their linear counterparts (4.0 – 7.4 h) contribute to their enhanced stability [24].”
BackgroundInfluentialCurrent status and potential role of circular RNAs in neurological disorders
Lu, S., Yang, X. F., Wang, C., Chen, S., Lu, S., Yan, W., Xiong, K., Liu, F., & Yan, J. (2019) · Journal of Neurochemistry · doi:10.1111/jnc.14724 · Cited by 57
Tian, T., Zhao, Y., Zheng, J., Jin, S., Liu, Z., & Wang, T. (2021) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2021.06.017 · Cited by 53
“4 h for their corresponding linear transcripts.(75) The steady-state levels of circRNAs were observed to be positively correlated with their nascent levels in cells with similar mitotic cycles, indicating that the detection of steady-state circRNAs in a cell- and/or tissue-specific manner likely reflects the endogenou…”
BackgroundCircular RNAs in cardiovascular diseases
Mei, X., & Chen, S. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107991 · Cited by 55
A module of inflammatory cytokines defines resistance of colorectal cancer to EGFR inhibitors
Gelfo, V., Rodia, M. T., Pucci, M., Dall’Ora, M., Santi, S., Solmi, R., Roth, L. E., Lindzen, M., Bonafè, M., Bertotti, A., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.12354 · Cited by 53
“Furthermore, co-treatment with Dexamethasone (DEX), a global inhibitor of the EGFR transcriptional response [7,28], dampened this production, pointing to a direct involvement of the EGFR pathway in the transcriptional induction of inflammatory mediators (Figure 4A).”
BackgroundSelf-citationLo, I., Hill, J., Vilhjálmsson, B. J., & Kjems, J. (2020) · RNA Biology · doi:10.1080/15476286.2020.1783487 · Cited by 53
“provides resistance to exonucleases, thereby increasing their half-life relative to linear transcripts [12], making circRNAs good potential targets for clinical use.”
BackgroundHost-derived circular RNAs display proviral activities in Hepatitis C virus-infected cells
Chen, T., Talló-Parra, M., Cao, Q. M., Kadener, S., Böttcher, R., Pérez‐Vilaró, G., Boonchuen, P., Somboonwiwat, K., Díez, J., & Sarnow, P. (2020) · PLoS Pathogens · doi:10.1371/journal.ppat.1008346 · Cited by 54
Ge, X., Xi, L., Wang, Q., Li, H., Xia, L., Cang, Z., Peng, W., & Huang, S. (2020) · Gene · doi:10.1016/j.gene.2020.144952 · Cited by 52
Effects of pericytes and colon cancer stem cells in the tumor microenvironment
Garza-Treviño, E. N., González, P. D., Salgado, C. I. V., & Garza, A. M. (2019) · Cancer Cell International · doi:10.1186/s12935-019-0888-9 · Cited by 53
The Role of ANRIL in Atherosclerosis
Razeghian‐Jahromi, I., Akhormeh, A. K., & Zibaeenezhad, M. J. (2022) · Disease Markers · doi:10.1155/2022/8859677 · Cited by 51
“Most of the circular RNAs are low in amount in relative to their targets [58, 59].”
BackgroundNie, D., Fu, J., Chen, H., Chen, H., & Fu, J. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20040861 · Cited by 51
“In addition to protein-coding potential, endogenous circular RNAs are resistant to exonuclease-mediated degradation and are presumably more stable than most linear RNAs in cells given the lack of its 5′ or 3′ ends [91,92].”
BackgroundD’Ambrosi, S., Visser, A., Antunes‐Ferreira, M., Poutsma, A., Giannoukakos, S., Sol, N., Sabrkhany, S., Bahce, I., Kuijpers, M. J. E., Egbrink, M. G. A. O., et al. (2021) · Cancers · doi:10.3390/cancers13184644 · Cited by 49
“As a result, circRNAs have an increased half-life, compared to linear RNAs, even in blood circulation [5,6].”
BackgroundCellular Trafficking of Nanotechnology‐Mediated mRNA Delivery
Huang, P., Deng, H., Wang, C., Zhou, Y., & Chen, X. S. (2023) · Advanced Materials · doi:10.1002/adma.202307822 · Cited by 53
Promising predictive molecular biomarkers for cervical cancer (Review)
Lizano, M., Carrillo‐García, A., la Cruz-Hernández, E. N. D., Castro-Muñoz, L. J., & Contreras‐Paredes, A. (2024) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2024.5374 · Cited by 50
“The covalently closed circular structure of circRNAs renders them resistant to exoribonucleases (176), which is advantageous when considering their usefulness as possible prognostic or predictive biomarkers. circRNAs exert their regulatory function through three main mechanisms: As sponges for…”
BackgroundNovel insights into the interaction between N6-methyladenosine modification and circular RNA
Xu, T., He, B., Sun, H., Xiong, M., Nie, J., Wang, S., & Pan, Y. (2022) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2022.01.007 · Cited by 48
Mao, Z., Wang, B., Zhang, T., & Cui, B. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-06265-2 · Cited by 51
Dávalos, A., Henriques, R., Latasa, M. J., Laparra, M., & Coca, M. A. (2019) · EFSA Supporting Publications · doi:10.2903/sp.efsa.2019.en-1688 · Cited by 50
“For example, circRNAs were found to be less abundant and dynamic than their counterparts (Enuka et al., 2016) .”
BackgroundInfluentialThe Expression, Functions and Mechanisms of Circular RNAs in Gynecological Cancers
Dong, P., Xu, D., Xiong, Y., Yue, J., Ihira, K., Konno, Y., & Watari, H. (2020) · Cancers · doi:10.3390/cancers12061472 · Cited by 46
“Due to their circular form and lack of free ends, circRNAs are resistant to RNA degradation by an exonuclease and have greater stability than linear RNAs [13].”
BackgroundThe nuclear DICER–circular RNA complex drives the deregulation of the glioblastoma cell microRNAome
Bronisz, A., Rooj, A. K., Krawczyński, K., Peruzzi, P., Salińska, E., Nakano, I., Purow, B., Chiocca, E. A., & Godlewski, J. (2020) · Science Advances · doi:10.1126/sciadv.abc0221 · Cited by 48
“CircRNAs have been shown to be long lived in vivo when compared to their linear counterparts, given that the bulk of RNA turnover involves exonucleases ( 17 ).”
Abere, B., Zhou, H., Li, J., Cao, S., Toptan, T., Grundhoff, A. T., Fischer, N., Moore, P. S., & Chang, Y. (2020) · mBio · doi:10.1128/mbio.03059-20 · Cited by 47
“the absence of free RNA ends (22, 27), MCV-encoded circMCV-T is sensitive to RNase R treatment, suggestive of linearization.”
BackgroundNoncoding RNAs in tumor metastasis: molecular and clinical perspectives
Liu, Q.-L., Zhang, Z., Wei, X., & Zhou, Z. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03929-0 · Cited by 47
Emerging roles of circular RNAs in liver cancer
Louis, C., Leclerc, D., & Coulouarn, C. (2021) · JHEP Reports · doi:10.1016/j.jhepr.2021.100413 · Cited by 46
Optimal design of synthetic circular RNAs
Choi, S.-W., & Nam, J. (2024) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01251-w · Cited by 45
“Researchers have found that the half-lives of circRNAs are, on average, two-to fourfold longer than those of linear mRNAs and sometimes as much as 10-fold longer 98 .”
BackgroundCircular RNAs as Potential Biomarkers and Therapeutic Targets for Metabolic Diseases
Zaiou, M. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-12668-1_10 · Cited by 44
Circular RNAs: Emblematic Players of Neurogenesis and Neurodegeneration
D’Anca, M., Buccellato, F. R., Fenoglio, C., & Galimberti, D. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23084134 · Cited by 44
“This is probably due to the resistance to degradation, favoring their concentration in aged tissue as the brain, dense with postmitotic cells [13].”
BackgroundWang, Q., Wang, H., Yan, H., Tian, H., Wang, Y., Yu, W., Dai, Z., Chen, P., Liu, Z., Tang, R., et al. (2022) · Science Advances · doi:10.1126/sciadv.abn3333 · Cited by 44
“An increasing number of circRNA functions have been revealed in the development of various cell types, and circRNAs have been shown to be ideal targets to regulate these processes (22).”
BackgroundDevelopment of Thermally Stable mRNA-LNP Delivery Systems: Current Progress and Future Prospects
Kafle, U., Truong, H. Q., Cao, T. G. N., & Meng, F. (2024) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.4c00826 · Cited by 47
Accentuating CircRNA-miRNA-Transcription Factors Axis: A Conundrum in Cancer Research
Singh, D., Kesharwani, P., Alhakamy, N. A., & Siddique, H. R. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.784801 · Cited by 43
“This covalently closed circular structure of circRNAs makes them stable against RNase digestion as compared to the linear RNAs (Enuka et al., 2016).”
BackgroundMechanisms of RNA export and nuclear retention
Khan, M. U., Hou, S., Chen, M., & Lei, H. (2022) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1755 · Cited by 43
“Most circRNAs have a length of 300–500 nt, contain 2–4 exons, and localize predominantly in the cytoplasm (Enuka et al., 2016).”
BackgroundCircular RNA discovery with emerging sequencing and deep learning technologies
Zhang, J., & Zhao, F. (2025) · Nature Genetics · doi:10.1038/s41588-025-02157-7 · Cited by 44
“Due to the greater stability of circRNAs versus mRNAs, a high circular-to-linear ratio may result from circRNA accumulation rather than active biogenesis 53 .”
Molecular Crosstalking among Noncoding RNAs: A New Network Layer of Genome Regulation in Cancer
Ragusa, M., Barbagallo, C., Brex, D., Caponnetto, A., Cirnigliaro, M., Battaglia, R., Barbagallo, D., Pietro, C. D., & Purrello, M. (2017) · International Journal of Genomics · doi:10.1155/2017/4723193 · Cited by 43
CircRNAs in tumor immunity and immunotherapy: Perspectives from innate and adaptive immunity
Yu, L., Xiao, Q., Yu, B., Lv, Q., Liu, Z., & Yin, J. (2023) · Cancer Letters · doi:10.1016/j.canlet.2023.216219 · Cited by 41
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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