Circular RNAs in Sudden Cardiac Death Related Diseases: Novel Biomarker for Clinical and Forensic Diagnosis
Abstract
:1. Introduction
2. Introduction of CircRNA
3. CircRNA Serves as Biomarkers in SCD-Related Diseases
3.1. Coronary Artery Disease
3.2. Myocardial Infarction
3.3. Myocardial Ischemia
3.4. Arrhythmias
3.5. Cardiomyopathy
3.6. Myocarditis
4. CircRNAs as Novel Biomarkers in Postmortem SCD Diagnosis
4.1. CircRNA Applications in Forensic Medicine
4.2. Current Biomarkers in Postmortem SCD Diagnosis
4.3. Opportunities and Challenges
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Osman, J.; Tan, S.C.; Lee, P.Y.; Low, T.Y.; Jamal, R. Sudden cardiac death (SCD)—Risk stratification and prediction with molecular biomarkers. J. Biomed. Sci. 2019, 26, 39. [Google Scholar] [CrossRef] [Green Version]
- Paratz, E.D.; Rowsell, L.; Zentner, D.; Parsons, S.; Morgan, N.; Thompson, T.; James, P.; Pflaumer, A.; Semsarian, C.; Smith, K.; et al. Cardiac arrest and sudden cardiac death registries: A systematic review of global coverage. Open Heart 2020, 7, e1195. [Google Scholar] [CrossRef]
- Wong, C.X.; Brown, A.; Lau, D.H.; Chugh, S.S.; Albert, C.M.; Kalman, J.M.; Sanders, P. Epidemiology of sudden cardiac death: Global and regional perspectives. Heart Lung Circ. 2019, 28, 6–14. [Google Scholar] [CrossRef] [Green Version]
- Isbister, J.; Semsarian, C. Sudden cardiac death: An update. Intern. Med. J. 2019, 49, 826–833. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kaneko, H.; Hara, M.; Mizutani, K.; Yoshiyama, M.; Yokoi, K.; Kabata, D.; Shintani, A.; Kitamura, T. Improving outcomes of witnessed out-of-hospital cardiac arrest after implementation of international liaison committee on resuscitation 2010 consensus: A nationwide prospective observational Population-Based study. J. Am. Heart Assoc. 2017, 6, e004959. [Google Scholar] [CrossRef]
- Lai, H.; Choong, C.V.; Fook-Chong, S.; Ng, Y.Y.; Finkelstein, E.A.; Haaland, B.; Goh, E.S.; Leong, B.S.; Gan, H.N.; Foo, D.; et al. Interventional strategies associated with improvements in survival for out-of-hospital cardiac arrests in Singapore over 10 years. Resuscitation 2015, 89, 155–161. [Google Scholar] [CrossRef] [PubMed]
- Kitamura, T.; Iwami, T.; Kawamura, T.; Nitta, M.; Nagao, K.; Nonogi, H.; Yonemoto, N.; Kimura, T. Nationwide improvements in survival from out-of-hospital cardiac arrest in Japan. Circulation 2012, 126, 2834–2843. [Google Scholar] [CrossRef] [Green Version]
- Bray, J.E.; di Palma, S.; Jacobs, I.; Straney, L.; Finn, J. Trends in the incidence of presumed cardiac out-of-hospital cardiac arrest in Perth, Western Australia, 1997–2010. Resuscitation 2014, 85, 757–761. [Google Scholar] [CrossRef] [PubMed]
- Grassi, S.; Campuzano, O.; Coll, M.; Brion, M.; Arena, V.; Iglesias, A.; Carracedo, A.; Brugada, R.; Oliva, A. Genetic variants of uncertain significance: How to match scientific rigour and standard of proof in sudden cardiac death? Leg. Med. 2020, 45, 101712. [Google Scholar] [CrossRef]
- Chen, J.H.; Inamori-Kawamoto, O.; Michiue, T.; Ikeda, S.; Ishikawa, T.; Maeda, H. Cardiac biomarkers in blood, and pericardial and cerebrospinal fluids of forensic autopsy cases: A reassessment with special regard to postmortem interval. Leg. Med. 2015, 17, 343–350. [Google Scholar] [CrossRef]
- Cao, Z.; Zhao, M.; Xu, C.; Zhang, T.; Jia, Y.; Wang, T.; Zhu, B. Diagnostic roles of postmortem cTn I and cTn T in cardiac death with special regard to myocardial infarction: A systematic literature review and Meta-Analysis. Int. J. Mol. Sci. 2019, 20, 3351. [Google Scholar] [CrossRef] [Green Version]
- Morin, D.P.; Homoud, M.K.; Estes, N.R. Prediction and prevention of sudden cardiac death. Card. Electrophysiol. Clin. 2017, 9, 631–638. [Google Scholar] [CrossRef] [PubMed]
- Sanger, H.L.; Klotz, G.; Riesner, D.; Gross, H.J.; Kleinschmidt, A.K. Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures. Proc. Natl. Acad. Sci. USA 1976, 73, 3852–3856. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hsiao, K.Y.; Sun, H.S.; Tsai, S.J. Circular RNA—New member of noncoding RNA with novel functions. Exp. Biol. Med. 2017, 242, 1136–1141. [Google Scholar] [CrossRef]
- Meng, X.; Li, X.; Zhang, P.; Wang, J.; Zhou, Y.; Chen, M. Circular RNA: An emerging key player in RNA world. Brief. Bioinform. 2017, 18, 547–557. [Google Scholar] [CrossRef] [PubMed]
- Nigro, J.M.; Cho, K.R.; Fearon, E.R.; Kern, S.E.; Ruppert, J.M.; Oliner, J.D.; Kinzler, K.W.; Vogelstein, B. Scrambled exons. Cell 1991, 64, 607–613. [Google Scholar] [CrossRef]
- Cocquerelle, C.; Daubersies, P.; Majerus, M.A.; Kerckaert, J.P.; Bailleul, B. Splicing with inverted order of exons occurs proximal to large introns. Embo. J. 1992, 11, 1095–1098. [Google Scholar] [CrossRef] [PubMed]
- Capel, B.; Swain, A.; Nicolis, S.; Hacker, A.; Walter, M.; Koopman, P.; Goodfellow, P.; Lovell-Badge, R. Circular transcripts of the testis-determining gene Sry in adult mouse testis. Cell 1993, 73, 1019–1030. [Google Scholar] [CrossRef]
- Lasda, E.; Parker, R. Circular RNAs: Diversity of form and function. RNA 2014, 20, 1829–1842. [Google Scholar] [CrossRef] [Green Version]
- Werfel, S.; Nothjunge, S.; Schwarzmayr, T.; Strom, T.M.; Meitinger, T.; Engelhardt, S. Characterization of circular RNAs in human, mouse and rat hearts. J. Mol. Cell. Cardiol. 2016, 98, 103–107. [Google Scholar] [CrossRef] [Green Version]
- Xu, T.; Wu, J.; Han, P.; Zhao, Z.; Song, X. Circular RNA expression profiles and features in human tissues: A study using RNA-seq data. BMC Genomics 2017, 18, 680. [Google Scholar] [CrossRef] [PubMed]
- Hansen, T.B.; Jensen, T.I.; Clausen, B.H.; Bramsen, J.B.; Finsen, B.; Damgaard, C.K.; Kjems, J. Natural RNA circles function as efficient microRNA sponges. Nature 2013, 495, 384–388. [Google Scholar] [CrossRef] [PubMed]
- Li, Z.; Huang, C.; Bao, C.; Chen, L.; Lin, M.; Wang, X.; Zhong, G.; Yu, B.; Hu, W.; Dai, L.; et al. Exon-intron circular RNAs regulate transcription in the nucleus. Nat. Struct. Mol. Biol. 2015, 22, 256–264. [Google Scholar] [CrossRef]
- Li, Z.; Huang, C.; Bao, C.; Chen, L.; Lin, M.; Wang, X.; Zhong, G.; Yu, B.; Hu, W.; Dai, L.; et al. Corrigendum: Exon-intron circular RNAs regulate transcription in the nucleus. Nat. Struct. Mol. Biol. 2017, 24, 194. [Google Scholar] [CrossRef] [PubMed]
- Luo, J.; Liu, H.; Luan, S.; Li, Z. Guidance of circular RNAs to proteins’ behavior as binding partners. Cell. Mol. Life Sci. 2019, 21, 4233–4243. [Google Scholar] [CrossRef]
- Wang, W.; Wang, Y.; Piao, H.; Li, B.; Huang, M.; Zhu, Z.; Li, D.; Wang, T.; Xu, R.; Liu, K. Circular RNAs as potential biomarkers and therapeutics for cardiovascular disease. PeerJ 2019, 7, e6831. [Google Scholar] [CrossRef] [PubMed]
- Ashwal-Fluss, R.; Meyer, M.; Pamudurti, N.R.; Ivanov, A.; Bartok, O.; Hanan, M.; Evantal, N.; Memczak, S.; Rajewsky, N.; Kadener, S. CircRNA biogenesis competes with pre-mRNA splicing. Mol. Cell. 2014, 56, 55–66. [Google Scholar] [CrossRef] [Green Version]
- Zhang, X.O.; Wang, H.B.; Zhang, Y.; Lu, X.; Chen, L.L.; Yang, L. Complementary sequence-mediated exon circularization. Cell 2014, 159, 134–147. [Google Scholar] [CrossRef] [Green Version]
- Jeck, W.R.; Sorrentino, J.A.; Wang, K.; Slevin, M.K.; Burd, C.E.; Liu, J.; Marzluff, W.F.; Sharpless, N.E. Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA 2013, 19, 141–157. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Altesha, M.A.; Ni, T.; Khan, A.; Liu, K.; Zheng, X. Circular RNA in cardiovascular disease. J. Cell. Physiol. 2019, 234, 5588–5600. [Google Scholar] [CrossRef]
- Conn, S.J.; Pillman, K.A.; Toubia, J.; Conn, V.M.; Salmanidis, M.; Phillips, C.A.; Roslan, S.; Schreiber, A.W.; Gregory, P.A.; Goodall, G.J. The RNA binding protein quaking regulates formation of circRNAs. Cell 2015, 160, 1125–1134. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, Y.; Xue, W.; Li, X.; Zhang, J.; Chen, S.; Zhang, J.L.; Yang, L.; Chen, L.L. The biogenesis of nascent circular RNAs. Cell Rep. 2016, 15, 611–624. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Khan, M.A.; Reckman, Y.J.; Aufiero, S.; van den Hoogenhof, M.M.; van der Made, I.; Beqqali, A.; Koolbergen, D.R.; Rasmussen, T.B.; van der Velden, J.; Creemers, E.E.; et al. RBM20 regulates circular RNA production from the titin gene. Circ. Res. 2016, 119, 996–1003. [Google Scholar] [CrossRef] [Green Version]
- Chen, I.; Chen, C.Y.; Chuang, T.J. Biogenesis, identification, and function of exonic circular RNAs. Wiley Interdiscip. Rev. RNA 2015, 6, 563–579. [Google Scholar] [CrossRef]
- Zhang, Y.; Zhang, X.O.; Chen, T.; ** genes, rRNAs, snRNAs, microRNAs and circRNAs as reference genes for the estimation of PMI. Forensic Sci. Med. Pathol. 2018, 14, 194–201. [Google Scholar] [CrossRef] [PubMed]
- Tu, C.; Du, T.; Ye, X.; Shao, C.; **e, J.; Shen, Y. Using miRNAs and circRNAs to estimate PMI in advanced stage. Leg. Med. 2019, 38, 51–57. [Google Scholar] [CrossRef] [PubMed]
- Liu, B.; Song, F.; Yang, Q.; Zhou, Y.; Shao, C.; Shen, Y.; Zhao, Z.; Tang, Q.; Hou, Y.; **e, J. Characterization of tissue-specific biomarkers with the expression of circRNAs in forensically relevant body fluids. Int. J. Leg. Med. 2019, 133, 1321–1331. [Google Scholar] [CrossRef] [PubMed]
- Gao, A. The screening of human tissue-specific circ RNAs molecules and its application in forensic medicine. Hebei Med. Univ. 2020, 69. (In Chinese) [Google Scholar]
- Zhang, Y.; Liu, B.; Shao, C.; Xu, H.; Xue, A.; Zhao, Z.; Shen, Y.; Tang, Q.; **e, J. Evaluation of the inclusion of circular RNAs in mRNA profiling in forensic body fluid identification. Int. J. Leg. Med. 2018, 132, 43–52. [Google Scholar] [CrossRef]
- Liu, B.; Yang, Q.; Meng, H.; Shao, C.; Jiang, J.; Xu, H.; Sun, K.; Zhou, Y.; Yao, Y.; Zhou, Z.; et al. Development of a multiplex system for the identification of forensically relevant body fluids. Forensic Sci. Int. Genet. 2020, 47, 102312. [Google Scholar] [CrossRef] [PubMed]
- Wang, J. Identification of age-correlated circ RNA markers for the development of forensic age estimation models. Hebei Med. Univ. 2020, 83. (In Chinese) [Google Scholar]
- Banon, R.; Hernandez-Romero, D.; Navarro, E.; Perez-Carceles, M.D.; Noguera-Velasco, J.A.; Osuna, E. Combined determination of B-type natriuretic peptide and high-sensitivity troponin I in the postmortem diagnosis of cardiac disease. Forensic Sci. Med. Pathol. 2019, 15, 528–535. [Google Scholar] [CrossRef] [PubMed]
- Carvajal-Zarrabal, O.; Hayward-Jones, P.M.; Nolasco-Hipolito, C.; Barradas-Dermitz, D.M.; Calderon-Garciduenas, A.L.; Lopez-Amador, N. Use of cardiac injury markers in the postmortem diagnosis of sudden cardiac death. J. Forensic Sci. 2017, 62, 1332–1335. [Google Scholar] [CrossRef]
- Madea, B.; Saukko, P.; Oliva, A.; Musshoff, F. Molecular pathology in forensic medicine—Introduction. Forensic Sci. Int. 2010, 203, 3–14. [Google Scholar] [CrossRef]
- Aljakna, A.; Fracasso, T.; Sabatasso, S. Molecular tissue changes in early myocardial ischemia: From pathophysiology to the identification of new diagnostic markers. Int. J. Leg. Med. 2018, 132, 425–438. [Google Scholar] [CrossRef]
- Arking, D.E.; Sotoodehnia, N. The genetics of sudden cardiac death. Annu. Rev. Genom. Hum. Genet. 2012, 13, 223–239. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ivanova, A.A.; Maksimov, V.N.; Orlov, P.S.; Ivanoshchuk, D.E.; Savchenko, S.V.; Voevoda, M.I. Association of the genetic markers for myocardial infarction with sudden cardiac death. Indian Heart J. 2017, 69, S8–S11. [Google Scholar] [CrossRef] [Green Version]
- Andersen, J.D.; Jacobsen, S.B.; Trudso, L.C.; Kampmann, M.L.; Banner, J.; Morling, N. Whole genome and transcriptome sequencing of post-mortem cardiac tissues from sudden cardiac death victims identifies a gene regulatory variant in NEXN. Int. J. Leg. Med. 2019, 133, 1699–1709. [Google Scholar] [CrossRef] [PubMed]
- Yang, Z.; Zhang, Q.; Yu, H.; Du, H.; Li, L.; He, Y.; Zhu, S.; Li, C.; Zhang, S.; Luo, B.; et al. Genetic association study of a novel indel polymorphism in HSPA1B with the risk of sudden cardiac death in the Chinese populations. Forensic Sci. Int. 2021, 318, 110637. [Google Scholar] [CrossRef] [PubMed]
- Lei, H.; Hu, J.; Sun, K.; Xu, D. The role and molecular mechanism of epigenetics in cardiac hypertrophy. Heart Fail. Rev. 2020, 1–10. [Google Scholar] [CrossRef]
- Pinchi, E.; Frati, P.; Aromatario, M.; Cipolloni, L.; Fabbri, M.; la Russa, R.; Maiese, A.; Neri, M.; Santurro, A.; Scopetti, M.; et al. MiR-1, miR-499 and miR-208 are sensitive markers to diagnose sudden death due to early acute myocardial infarction. J. Cell. Mol. Med. 2019, 23, 6005–6016. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shomanova, Z.; Ohnewein, B.; Schernthaner, C.; Hofer, K.; Pogoda, C.A.; Frommeyer, G.; Wernly, B.; Brandt, M.C.; Dieplinger, A.M.; Reinecke, H.; et al. Classic and novel biomarkers as potential predictors of ventricular arrhythmias and sudden cardiac death. J. Clin. Med. 2020, 9, 578. [Google Scholar] [CrossRef] [Green Version]
- Ondruschka, B.; Woydt, L.; Bernhard, M.; Franke, H.; Kirsten, H.; Loffler, S.; Pohlers, D.; Hammer, N.; Dressler, J. Post-mortem in situ stability of serum markers of cerebral damage and acute phase response. Int. J. Leg. Med. 2019, 133, 871–881. [Google Scholar] [CrossRef] [PubMed]
- Woydt, L.; Bernhard, M.; Kirsten, H.; Burkhardt, R.; Hammer, N.; Gries, A.; Dressler, J.; Ondruschka, B. Intra-individual alterations of serum markers routinely used in forensic pathology depending on increasing post-mortem interval. Sci. Rep. 2018, 8, 12811. [Google Scholar] [CrossRef]
- Maeda, H.; Zhu, B.L.; Ishikawa, T.; Quan, L.; Michiue, T. Significance of postmortem biochemistry in determining the cause of death. Leg. Med. 2009, 1, S46–S49. [Google Scholar] [CrossRef] [PubMed]
- Lv, Y.; Li, S.; Li, Z.; Tao, R.; Shao, Y.; Chen, Y. Quantitative analysis of noncoding RNA from paired fresh and formalin-fixed paraffin-embedded brain tissues. Int. J. Leg. Med. 2020, 134, 873–884. [Google Scholar] [CrossRef]
Diseases | Species | Samples | Sample Capacity | Technique | Expression Regulation | Representative CircRNAs | Reference | ||
---|---|---|---|---|---|---|---|---|---|
Case/Control | DE | UR | DR | ||||||
CAD | human | PBMC | 70/30 | sequence | 2368 | 2283 | 85 | hsa_circ_0003915, hsa_circ_001272, hsa_circ_0103771, hsa_circ_0006251, hsa_circ_0066529, hsa_circ_0030042 | [46] |
CAD | human | PB | 20/20 | microarray | 110 | 73 | 37 | hsa_circ_0030769, hsa_circ_0079828, hsa_circ_15486-161, hsa_circ_0122274, hsa_circ_16316-13, hsa_circ_0140538 | [47] |
CAD | human | PB | 5/5 | microarray | 3423 | - | - | hsa_circ_0125589, hsa_circ_0001946, hsa_circ_0008507 | [48] |
CAD | human | PB | 12/12 | microarray | 22 | 12 | 10 | hsa_circ_0082081, hsa_circ_0113854, hsa_circ_0124644, hsa_circ_0098964, hsa-circRNA5974-1 | [49] |
CAD | human | PBMC | 24/7 | microarray | 795 | 624 | 171 | hsa_circ_0001879, hsa_circ_0004104, hsa_circ_004432 | [50] |
CAD | human | PB | 6/6 | microarray | 40 | 13 | 27 | hsa_circRNA11783-2, hsa_circRNA6510-1 | [51] |
MI | mouse | Myo | 2/2 | microarray | 82 | 41 | 41 | mmu_circ_0001113 | [52] |
MIR | rat | Myo | 2/2 | sequencing | 69 | 36 | 33 | rno_circ_0000112, rno_circ_0005562, rno_circ_0008515 | [53] |
MIR | mouse | Myo | 3/3 | sequencing | 21 | 14 | 7 | novel_circ_0020886, novel_circ_0008516, novel_circ_0002498 | [54] |
MIR | mouse | Myo | 1/1 | microarray | - | - | - | mmu_circ_006636 | [55] |
MIR | mouse | PCM | 1/1 | microarray | - | - | - | mmu_circ_400095, mmu_circ_101512, mmu_circ_100714, mmu_circ_405755, mmu_circ_101237 | [56] |
AF | human | Myo | 3/3 | microarray | 736 | 537 | 199 | hsa_circ_100612, hsa_circ_405917 | [57] |
AF | human | Atr | 7/7 | sequencing | 280 | 46 | 234 | hsa_circ_24801, hsa_circ_16247 | [58] |
AF | human | left-Atr | 8/6 | sequencing | 40 | - | - | hsa_circ_0025470, hsa_circ_0035132, hsa_circ_0035148, hsa_circ_0057344, hsa_circ_0112651, hsa_circ_0112664 | [59] |
AF | human | Atr | 9/6 | sequencing | 108 | 51 | 57 | hsa_circ_20118, hsa_circ_17558, hsa_circ_16688 ,hsa_circ_11109, hsa_circ_11017, hsa_circ_11058 | [60] |
AF | human | Atr | 9/6 | sequencing | 147 | 102 | 45 | hsa_circ_0005643, novcl_circ_0026284, novel_circ_0077334, novel_circ_0046852, novel_circ_0068696, novel _circ_0055884 | [61] |
AF | human | Atr | 10/10 | sequencing | 478 (left) | 374 | 104 | hsa_circ_0004270, hsa_circ_0000075, hsa_circ_0030254, hsa_circ_0007271, chr6:129371063-129419560 | [62] |
535 (right) | 267 | 268 | |||||||
23 (both) | 20 | 3 | |||||||
AF | human | Atr | 4/4 | sequencing | 296 | 238 | 58 | hsa_circ_002085, hsa_circ_001321 | [63] |
AF | human | blood | 15/15 | microarray | 31 | 24 | 7 | hsa_circ_025016, hsa_circ_404686, hsa_circR_000367, hsa_circ_001729, hsa_circ_100790, hsa_circ_030162, hsa_circ_100789, hsa_circ_104270, hsa_circ_102049 | [64] |
HCM | human | LV | 2/2 | sequencing | 60 | 34 | 26 | hsa_circ_0003101, chr9:108484902-108467878 | [33] |
DCM | human | LV | 2/2 | sequencing | 43 | 15 | 28 | chr4:121675708-121732604, chr2:179542852-179586861 | [33] |
DCM | human | hiPSC-CMs | 26 1 | sequencing | - | - | - | circNCX1, circCHD7, circATXN10, circDNAJ6C | [65] |
DOXIC | human | Myo | 10/17 2 | microarray | - | - | - | hsa_circ_0004214 | [66] |
DOXIC | human | Myo | 3/3 | sequencing | 356 | 207 | 149 | hsa_circ_0001141 | [67] |
diabetic CM | mouse | Myo | 4/4 | microarray | 43 | 24 | 19 | mmu_circ_010567 | [68] |
diabetic CM | mouse | Myo | 4/4 | microarray | 76 | 45 | 31 | mmu_circ_000203 | [69] |
ACM | mouse | Myo | 3/3 | microarray | 265 | 114 | 151 | mmu_circ_011978, mmu_circ_011979, mmu_circ_011977, mmu_circ_011982, mmu_circ_011976, mmu_circ_011975, | [70] |
fulminant myocarditis | human | PB | 3/3 | microarray | 3172 | 2281 | 892 | hsa_circ_0071542, hsa_circ_0014350, hsa_circ_0073029 | [71] |
Diseases | CircRNA | Samples | Sample Capacity | Expression Regulation | AUC (95% CI) | Sensitivity | Specificity | p-Value | Reference |
---|---|---|---|---|---|---|---|---|---|
Case/Control | |||||||||
CAD | hsa_circ_0001946 | PBL | 100/100 | up | 0.71 (0.64–0.79) | 0.85 | 0.52 | - | [48] |
CAD | hsa_circ_0000284 | PBL | 100/100 | up | 0.68 (0.61–0.76) | 0.66 | 0.71 | - | [48] |
CAD | hsa_circ_0008507 | PBL | 100/100 | up | 0.75 (0.68–0.82) | 0.86 | 0.60 | - | [48] |
CAD | hsa_circ_0124644 | PB | 115/137 | up | 0.872 (0.785–0.960) | 0.867 | 0.767 | <0.001 | [49] |
CAD | hsa_circ_0082081 | PB | 115/137 | up | 0.66 (0.522–0.798) | 0.833 | 0.433 | 0.033 | [49] |
CAD | hsa_circ_0113854 | PB | 115/137 | up | 0.689 (0.555–0.823) | 0.867 | 0.50 | 0.012 | [49] |
CAD | hsa_circ_0098964 | PB | 115/137 | up | 0.82 (0.707–0.933) | 0.80 | 0.867 | <0.001 | [49] |
CAD | hsa_circRNA5974-1 | PB | 115/137 | up | 0.743 (0.619–0.867) | 0.633 | 0.733 | 0.001 | [49] |
CAD | hsa_circ_0001879 | PBMC | 412/290 | up | 0.703 (0.656–0.750) | 0.831 | 0.543 | <0.001 | [50] |
CAD | hsa_circ_0004104 | PBMC | 412/290 | up | 0.700 (90.646–0.755) | 0.707 | 0.614 | <0.001 | [50] |
CAD | hsa_circRNA11783-2 | PBMC | 60/81 | down | - | - | - | - | [51] |
CAD | hsa_circ_0001445 | PB | 74/1261 | down | 0.589 (0.506–0.671) | - | - | < 0.001 | [75] |
CAD | hsa_circ_0041103 | PBMC | 342/246 | down | 0.62 (0.57–0.67) | 0.60 | 0.61 | <0.001 | [76] |
AF | hsa_circ_025016 | plasma | 75/295 | up | 0.802 (0.798–0.806) | 0.794 | 0.776 | <0.001 | [64] |
HCM | circDNAJC6 | serum | 64/53 | down | 0.819 (0.725–0.912) | - | - | <0.001 | [78] |
HCM | circTMEM56 | serum | 64/53 | down | 0.738 (0.621–0.856) | - | - | <0.001 | [78] |
HCM | circMBOAT2 | serum | 64/53 | down | 0.756 (0.653–0.860) | - | - | <0.001 | [78] |
CircRNAs | Samples | Sample Capacity | Expression | Functions | Reference |
---|---|---|---|---|---|
Case/Control | Regulation | ||||
mmu_circ_0001113 | 3 d post-MI mice heart | 5/8 | down | induces cardiomyocyte apoptosis and reduce neovascularization | [52] |
hsa_circ_0000615 | MI patient whole blood | 327/86 | down | predicts of LV dysfunction, improves risk classification after MI | [81] [82] |
circACAP2 | MI rat heart | -/- | up | promotes apoptosis | [84] |
mmu_circ_0001878 | 24 h post MI mice heart | 10/10 | up | overexpression in vivo increased cardiac infarct size | [86] |
rno_circ_002317 | 5 w post-MI rats heart | 8/6 | up | restrains ischemic cardiac injury | [87] |
mmu_circ_0001258 | 3 d post-MI mice heart | 6/6 | down | impairs the progression of AMI by modulating the miR-500b-5p/EMP1 axis | [88] |
mmu_circ_0001704 | 7 d post-MI mice heart | 6/6 | down | downregulation of it promotes cardiomyocyte proliferation and angiogenesis, and inhibits cardiomyocyte apoptosis after MI | [89] |
Disease Models | CircRNAs | Samples | Sample Capacity | Expression Regulation | Functions | Reference |
---|---|---|---|---|---|---|
Case/Control | ||||||
myocardial ischemia | mmu_circ_004295 | 30 min ischemia of mouse heart | 6/6 | up | promotes cardiomyocyte apoptosis | [90] |
myocardial ischemia | hsa_circ_0007623 | ISO intraperitoneally injected of mouse heart | 6/6 | up | promotes myocardial repair and improves cardiac function | [93] |
MIR | mmu_circ_006636 | 60 min ischemia follow 3 h/1 h reperfusion mice heart | 6/6 | down | protects the heart from ischemia/reperfusion injury and reduces myocardial infarct sizes | [55] |
MIR | mmu_circ_101237 | primary cardiomyocyte of mice | 3/3 | up | attenuates autophagy and cell death in cardiomyocytes, and reduces myocardial infarct size | [56] |
MIR | hsa_circ_0060180 | acute ischemic stroke patients plasma | 26/26 | down | participates in apoptosis | [91] |
OGD | hsa_circ_0002142 | acute myocardial ischemia human blood | 25/25 | up | enhances OGD-induced cell viability and migration, but declines OGD-induced apoptosis | [94] |
OGD | rno_circ_009421 | rats H9c2 cells | 3/3 | up | releases OGD-induced damage and down-regulates apoptosis and autophagy | [95] |
OGD | hsa_circ_0010729 | human cardiomyocytes | 3/3 | up | silence of it could help protect cardiomyocytes from ischemic injury | [96] |
CircRNAs | Samples | Sample Capacity | Expression | Reference |
---|---|---|---|---|
Case/Control | Regulation | |||
hsa_circ_100612, hsa_circ_405917 | human left atrial appendages | 3/3 | down | [57] |
hsa_circ_008132, hsa_circ_104052, hsa_circ_101021, hsa_circ_101020, hsa_circ_102341, hsa_circ_404747, hsa_circ_002641, hsa_circ_079477 | human left atrial appendages | 3/3 | up | [57] |
hsa_circ_16247, hsa_circ_24801 | human atrial tissues | 35/35 | up | [58] |
hsa_circ_0005643, novcl_circ_0026284, novel_circ_0077334, novel_circ_0068696, novel_circ_0055884 | human atrial tissues | 15/15 | up | [61] |
Diseases | CircRNA | Samples | Sample Capacity | Expression Regulation | Functions | Reference |
---|---|---|---|---|---|---|
Case/Control | ||||||
ICM | hsa_circ_0006156 | human heart tissues | 7/4 | down | reduces left ventricular functions | [52] |
DCM | circNCX1 ratio 1, circCHD7 ratio, circATXN10 ratio | human heart tissues | 8/8 | up | - | [65] |
DCM | circDNAJ6C ratio | human heart tissues | 8/8 | down | - | [65] |
DOXIC | hsa_circ_0004214 | mouse heart tissues | 10/10 | down | educes the enlarged left ventricle, and facilitates nuclear translocation of AKT and PDK1 | [66] |
DOXIC | hsa_circ_0001141 | human heart tissues | 3/3 | up | ameliorates DOX-induced cardiomyocyte injury and dysfunction | [67] |
Diabetic CM | hsa_circ_0076631 | diabetic patient serum | 10/10 | up | mediates pyroptosis of diabetic cardiomyopathy by functioning as a competing endogenous RNA | [103] |
Diabetic CM | mmu_circ_010567 | mouse heart tissues | 10/10 | up | participates in the pathogenesis of myocardial fibrosis | [68] |
Diabetic CM | mmu_circ_000203 | mouse heart tissues | 8/8 | up | enhances the expression of fibrosis-associated genes by depressing targets of miR-26b-5p, Col1a2 and CTGF, in cardiac fibroblasts | [69] |
fulminant myocarditis | hsa_circ_0071542 | human heart tissues | 8/8 | up | may be associated with the severity of fulminant myocarditis | [71] |
myocarditis | circANKRD36 | rats H9c2 cells | 3/3 | up | silencing it alleviates apoptosis and inflammatory injury induced by lipopolysaccharide | [105] |
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Tian, M.; Cao, Z.; Pang, H. Circular RNAs in Sudden Cardiac Death Related Diseases: Novel Biomarker for Clinical and Forensic Diagnosis. Molecules 2021, 26, 1155. https://doi.org/10.3390/molecules26041155
Tian M, Cao Z, Pang H. Circular RNAs in Sudden Cardiac Death Related Diseases: Novel Biomarker for Clinical and Forensic Diagnosis. Molecules. 2021; 26(4):1155. https://doi.org/10.3390/molecules26041155
Chicago/Turabian StyleTian, Meihui, Zhipeng Cao, and Hao Pang. 2021. "Circular RNAs in Sudden Cardiac Death Related Diseases: Novel Biomarker for Clinical and Forensic Diagnosis" Molecules 26, no. 4: 1155. https://doi.org/10.3390/molecules26041155