Skip to main content

Advertisement

SpringerLink
Log in

circRNA is a potential target for cardiovascular diseases treatment

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Circular RNAs (circRNAs), a novel class of endogenous noncoding RNA, are characterized by their covalently closed-loop structures without a 5′ cap or a 3′ poly(A) tail. With the evolution of high-throughput sequencing technology and bioinformatics, an increasing number of circRNAs have been discovered, and their functions were highlighted. Cardiovascular diseases (CVDs) have become the world’s leading killers, with serious impacts on human health. Although significant progress has been made in clarifying the development of CVDs from the molecular to the cellular level, CVDs remain one of the leading causes of death in humans. circRNAs mainly function as a “sponge” to absorb microRNAs, which results in the positive control of downstream proteins. They play important regulatory roles in the development of CVDs. This paper reviews current knowledge on the biogenesis, detection and validation, translation, translocation and degradation, and general functions of circRNAs, with a focus on their roles in CVDs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Li M, Ding W, Tariq MA, Chang W, Zhang X, Xu W, Hou L, Wang Y, Wang J (2018) A circular transcript of ncx1 gene mediates ischemic myocardial injury by targeting miR-133a-3p. Theranostics 8:5855–5869. https://doi.org/10.7150/thno.27285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Karra R, Poss KD (2017) Redirecting cardiac growth mechanisms for therapeutic regeneration. J Clin Invest 127:427–436. https://doi.org/10.1172/JCI89786

    Article  PubMed  PubMed Central  Google Scholar 

  3. Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, Maier L, Mackowiak SD, Gregersen LH, Munschauer M, Loewer A, Ziebold U, Landthaler M, Kocks C, le Noble F, Rajewsky N (2013) Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 495:333–338. https://doi.org/10.1038/nature11928

    Article  CAS  PubMed  Google Scholar 

  4. Sanger HL, Klotz G, Riesner D, Gross HJ, Kleinschmidt AK (1976) Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures. Proc Natl Acad Sci USA 73:3852–3856. https://doi.org/10.1073/pnas.73.11.3852

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Jeck WR, Sorrentino JA, Wang K, Slevin MK, Burd CE, Liu J, Marzluff WF, Sharpless NE (2013) Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA 19:141–157. https://doi.org/10.1261/rna.035667.112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Chen LL (2016) The biogenesis and emerging roles of circular RNAs. Nat Rev Mol Cell Biol 17:205–211. https://doi.org/10.1038/nrm.2015.32

    Article  CAS  PubMed  Google Scholar 

  7. Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, Kjems J (2013) Natural RNA circles function as efficient microRNA sponges. Nature 495:384–388. https://doi.org/10.1038/nature11993

    Article  CAS  PubMed  Google Scholar 

  8. Zang J, Lu D, Xu A (2020) The interaction of circRNAs and RNA binding proteins: an important part of circRNA maintenance and function. J Neurosci Res 98:87–97. https://doi.org/10.1002/jnr.24356

    Article  CAS  PubMed  Google Scholar 

  9. Du WW, Yang W, Liu E, Yang Z, Dhaliwal P, Yang BB (2016) Foxo3 circular RNA retards cell cycle progression via forming ternary complexes with p21 and CDK2. Nucleic Acids Res 44:2846–2858. https://doi.org/10.1093/nar/gkw027

    Article  PubMed  PubMed Central  Google Scholar 

  10. Legnini I, Di Timoteo G, Rossi F, Morlando M, Briganti F, Sthandier O, Fatica A, Santini T, Andronache A, Wade M, Laneve P, Rajewsky N, Bozzoni I (2017) Circ-ZNF609 Is a circular RNA that can be translated and functions in myogenesis. Mol Cell 66(22–37):e9. https://doi.org/10.1016/j.molcel.2017.02.017

    Article  CAS  Google Scholar 

  11. Zhang Y, Zhang XO, Chen T, Xiang JF, Yin QF, Xing YH, Zhu S, Yang L, Chen LL (2013) Circular intronic long noncoding RNAs. Mol Cell 51:792–806. https://doi.org/10.1016/j.molcel.2013.08.017

    Article  CAS  PubMed  Google Scholar 

  12. Gao J, Chen X, Shan C, Wang Y, Li P, Shao K (2021) Autophagy in cardiovascular diseases: role of noncoding RNAs. Mol Ther Nucleic Acids 23:101–118. https://doi.org/10.1016/j.omtn.2020.10.039

    Article  CAS  PubMed  Google Scholar 

  13. Dong R, Ma XK, Chen LL, Yang L (2017) Increased complexity of circRNA expression during species evolution. RNA Biol 14:1064–1074. https://doi.org/10.1080/15476286.2016.1269999

    Article  PubMed  Google Scholar 

  14. Piwecka M, Glazar P, Hernandez-Miranda LR, Memczak S, Wolf SA, Rybak-Wolf A, Filipchyk A, Klironomos F, Cerda Jara CA, Fenske P, Trimbuch T, Zywitza V, Plass M, Schreyer L, Ayoub S, Kocks C, Kuhn R, Rosenmund C, Birchmeier C, Rajewsky N (2017) Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function. Science. https://doi.org/10.1126/science.aam8526

    Article  PubMed  Google Scholar 

  15. Rybak-Wolf A, Stottmeister C, Glazar P, Jens M, Pino N, Giusti S, Hanan M, Behm M, Bartok O, Ashwal-Fluss R, Herzog M, Schreyer L, Papavasileiou P, Ivanov A, Ohman M, Refojo D, Kadener S, Rajewsky N (2015) Circular RNAs in the mammalian brain are highly abundant, conserved, and dynamically expressed. Mol Cell 58:870–885. https://doi.org/10.1016/j.molcel.2015.03.027

    Article  CAS  PubMed  Google Scholar 

  16. Jeck WR, Sharpless NE (2014) Detecting and characterizing circular RNAs. Nat Biotechnol 32:453–461. https://doi.org/10.1038/nbt.2890

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Panda AC, De S, Grammatikakis I, Munk R, Yang X, Piao Y, Dudekula DB, Abdelmohsen K, Gorospe M (2017) High-purity circular RNA isolation method (RPAD) reveals vast collection of intronic circRNAs. Nucleic Acids Res 45:e116. https://doi.org/10.1093/nar/gkx297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Yang Y, Fan X, Mao M, Song X, Wu P, Zhang Y, Jin Y, Yang Y, Chen LL, Wang Y, Wong CC, Xiao X, Wang Z (2017) Extensive translation of circular RNAs driven by N(6)-methyladenosine. Cell Res 27:626–641. https://doi.org/10.1038/cr.2017.31

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Chen RX, Chen X, Xia LP, Zhang JX, Pan ZZ, Ma XD, Han K, Chen JW, Judde JG, Deas O, Wang F, Ma NF, Guan X, Yun JP, Wang FW, Xu RH, Dan X (2019) N(6)-methyladenosine modification of circNSUN2 facilitates cytoplasmic export and stabilizes HMGA2 to promote colorectal liver metastasis. Nat Commun 10:4695. https://doi.org/10.1038/s41467-019-12651-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Park OH, Ha H, Lee Y, Boo SH, Kwon DH, Song HK, Kim YK (2019) Endoribonucleolytic cleavage of m(6)A-containing RNAs by RNase P/MRP complex. Mol Cell 74(494–507):e8. https://doi.org/10.1016/j.molcel.2019.02.034

    Article  CAS  Google Scholar 

  21. Jia R, Xiao MS, Li Z, Shan G, Huang C (2019) Defining an evolutionarily conserved role of GW182 in circular RNA degradation. Cell Discov 5:45. https://doi.org/10.1038/s41421-019-0113-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Huang C, Liang D, Tatomer DC, Wilusz JE (2018) A length-dependent evolutionarily conserved pathway controls nuclear export of circular RNAs. Genes Dev 32:639–644. https://doi.org/10.1101/gad.314856.118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Lu Q, Liu T, Feng H, Yang R, Zhao X, Chen W, Jiang B, Qin H, Guo X, Liu M, Li L, Guo H (2019) Circular RNA circSLC8A1 acts as a sponge of miR-130b/miR-494 in suppressing bladder cancer progression via regulating PTEN. Mol Cancer 18:111. https://doi.org/10.1186/s12943-019-1040-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kristensen LS, Hansen TB, Veno MT, Kjems J (2018) Circular RNAs in cancer: opportunities and challenges in the field. Oncogene 37:555–565. https://doi.org/10.1038/onc.2017.361

    Article  CAS  PubMed  Google Scholar 

  25. Zheng Q, Bao C, Guo W, Li S, Chen J, Chen B, Luo Y, Lyu D, Li Y, Shi G, Liang L, Gu J, He X, Huang S (2016) Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs. Nat Commun 7:11215. https://doi.org/10.1038/ncomms11215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Chen N, Zhao G, Yan X, Lv Z, Yin H, Zhang S, Song W, Li X, Li L, Du Z, Jia L, Zhou L, Li W, Hoffman AR, Hu JF, Cui J (2018) A novel FLI1 exonic circular RNA promotes metastasis in breast cancer by coordinately regulating TET1 and DNMT1. Genome Biol 19:218. https://doi.org/10.1186/s13059-018-1594-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Hsiao KY, Lin YC, Gupta SK, Chang N, Yen L, Sun HS, Tsai SJ (2017) Noncoding effects of circular RNA CCDC66 promote colon cancer growth and metastasis. Cancer Res 77:2339–2350. https://doi.org/10.1158/0008-5472.CAN-16-1883

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Verduci L, Ferraiuolo M, Sacconi A, Ganci F, Vitale J, Colombo T, Paci P, Strano S, Macino G, Rajewsky N, Blandino G (2017) The oncogenic role of circPVT1 in head and neck squamous cell carcinoma is mediated through the mutant p53/YAP/TEAD transcription-competent complex. Genome Biol 18:237. https://doi.org/10.1186/s13059-017-1368-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Capel B, Swain A, Nicolis S, Hacker A, Walter M, Koopman P, Goodfellow P, Lovell-Badge R (1993) Circular transcripts of the testis-determining gene Sry in adult mouse testis. Cell 73:1019–1030. https://doi.org/10.1016/0092-8674(93)90279-y

    Article  CAS  PubMed  Google Scholar 

  30. Yu CY, Li TC, Wu YY, Yeh CH, Chiang W, Chuang CY, Kuo HC (2017) The circular RNA circBIRC6 participates in the molecular circuitry controlling human pluripotency. Nat Commun 8:1149. https://doi.org/10.1038/s41467-017-01216-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Li X, Liu CX, Xue W, Zhang Y, Jiang S, Yin QF, Wei J, Yao RW, Yang L, Chen LL (2017) Coordinated circRNA biogenesis and function with NF90/NF110 in viral infection. Mol Cell 67:214-227.e7. https://doi.org/10.1016/j.molcel.2017.05.023

    Article  CAS  PubMed  Google Scholar 

  32. Ashwal-Fluss R, Meyer M, Pamudurti NR, Ivanov A, Bartok O, Hanan M, Evantal N, Memczak S, Rajewsky N, Kadener S (2014) circRNA biogenesis competes with pre-mRNA splicing. Mol Cell 56:55–66. https://doi.org/10.1016/j.molcel.2014.08.019

    Article  CAS  PubMed  Google Scholar 

  33. Meyer KD, Patil DP, Zhou J, Zinoviev A, Skabkin MA, Elemento O, Pestova TV, Qian SB, Jaffrey SR (2015) 5’ UTR m(6)A promotes cap-independent translation. Cell 163:999–1010. https://doi.org/10.1016/j.cell.2015.10.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. van Heesch S, Witte F, Schneider-Lunitz V, Schulz JF, Adami E, Faber AB, Kirchner M, Maatz H, Blachut S, Sandmann CL, Kanda M, Worth CL, Schafer S, Calviello L, Merriott R, Patone G, Hummel O, Wyler E, Obermayer B, Mucke MB, Lindberg EL, Trnka F, Memczak S, Schilling M, Felkin LE, Barton PJR, Quaife NM, Vanezis K, Diecke S, Mukai M, Mah N, Oh SJ, Kurtz A, Schramm C, Schwinge D, Sebode M, Harakalova M, Asselbergs FW, Vink A, de Weger RA, Viswanathan S, Widjaja AA, Gartner-Rommel A, Milting H, Dos Remedios C, Knosalla C, Mertins P, Landthaler M, Vingron M, Linke WA, Seidman JG, Seidman CE, Rajewsky N, Ohler U, Cook SA, Hubner N (2019) The translational landscape of the human heart. Cell 178(242–260):e29. https://doi.org/10.1016/j.cell.2019.05.010

    Article  CAS  Google Scholar 

  35. Werfel S, Nothjunge S, Schwarzmayr T, Strom TM, Meitinger T, Engelhardt S (2016) Characterization of circular RNAs in human, mouse and rat hearts. J Mol Cell Cardiol 98:103–107. https://doi.org/10.1016/j.yjmcc.2016.07.007

    Article  CAS  PubMed  Google Scholar 

  36. Wu G, Zhou W, Pan X, Sun Z, Sun Y, Xu H, Shi P, Li J, Gao L, Tian X (2020) Circular RNA profiling reveals exosomal circ_0006156 as a novel biomarker in papillary thyroid cancer. Mol Ther Nucleic Acids 19:1134–1144. https://doi.org/10.1016/j.omtn.2019.12.025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Wang Y, Zhao R, Liu W, Wang Z, Rong J, Long X, Liu Z, Ge J, Shi B (2019) Exosomal circHIPK3 released from hypoxia-pretreated cardiomyocytes regulates oxidative damage in cardiac microvascular endothelial cells via the miR-29a/IGF-1 pathway. Oxid Med Cell Longev 2019:7954657. https://doi.org/10.1155/2019/7954657

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Mendis S, Davis S, Norrving B (2015) Organizational update: the world health organization global status report on noncommunicable diseases 2014; one more landmark step in the combat against stroke and vascular disease. Stroke 46:e121–e122. https://doi.org/10.1161/STROKEAHA.115.008097

    Article  PubMed  Google Scholar 

  39. Jakobi T, Czaja-Hasse LF, Reinhardt R, Dieterich C (2016) Profiling and validation of the circular RNA repertoire in adult murine hearts. Genomics Proteom Bioinform 14:216–223. https://doi.org/10.1016/j.gpb.2016.02.003

    Article  Google Scholar 

  40. Aaronson KD, Sackner-Bernstein J (2006) Risk of death associated with nesiritide in patients with acutely decompensated heart failure. JAMA 296:1465–1466. https://doi.org/10.1001/jama.296.12.1465

    Article  CAS  PubMed  Google Scholar 

  41. Tham YK, Bernardo BC, Ooi JY, Weeks KL, McMullen JR (2015) Pathophysiology of cardiac hypertrophy and heart failure: signaling pathways and novel therapeutic targets. Arch Toxicol 89:1401–1438. https://doi.org/10.1007/s00204-015-1477-x

    Article  CAS  PubMed  Google Scholar 

  42. Nakamura M, Sadoshima J (2018) Mechanisms of physiological and pathological cardiac hypertrophy. Nat Rev Cardiol 15:387–407. https://doi.org/10.1038/s41569-018-0007-y

    Article  CAS  PubMed  Google Scholar 

  43. Jahn C, Bar C, Thum T (2019) CircSlc8a1, breaking a vicious circle in cardiac hypertrophy. Cardiovasc Res 115:1946–1947. https://doi.org/10.1093/cvr/cvz147

    Article  CAS  PubMed  Google Scholar 

  44. Lim TB, Aliwarga E, Luu TDA, Li YP, Ng SL, Annadoray L, Sian S, Ackers-Johnson MA, Foo RS (2019) Targeting the highly abundant circular RNA circSlc8a1 in cardiomyocytes attenuates pressure overload induced hypertrophy. Cardiovasc Res 115:1998–2007. https://doi.org/10.1093/cvr/cvz130

    Article  CAS  PubMed  Google Scholar 

  45. Li H, Xu JD, Fang XH, Zhu JN, Yang J, Pan R, Yuan SJ, Zeng N, Yang ZZ, Yang H, Wang XP, Duan JZ, Wang S, Luo JF, Wu SL, Shan ZX (2020) Circular RNA circRNA_000203 aggravates cardiac hypertrophy via suppressing miR-26b-5p and miR-140-3p binding to Gata4. Cardiovasc Res 116:1323–1334. https://doi.org/10.1093/cvr/cvz215

    Article  CAS  PubMed  Google Scholar 

  46. Wang K, Long B, Liu F, Wang JX, Liu CY, Zhao B, Zhou LY, Sun T, Wang M, Yu T, Gong Y, Liu J, Dong YH, Li N, Li PF (2016) A circular RNA protects the heart from pathological hypertrophy and heart failure by targeting miR-223. Eur Heart J 37:2602–2611. https://doi.org/10.1093/eurheartj/ehv713

    Article  CAS  PubMed  Google Scholar 

  47. Xu X, Wang J, Wang X (2020) Silencing of circHIPK3 inhibits pressure overload-induced cardiac hypertrophy and dysfunction by sponging miR-185-3p. Drug Des Dev Ther 14:5699–5710. https://doi.org/10.2147/DDDT.S245199

    Article  CAS  Google Scholar 

  48. Holdt LM, Teupser D (2012) Recent studies of the human chromosome 9p21 locus, which is associated with atherosclerosis in human populations. Arterioscler Thromb Vasc Biol 32:196–206. https://doi.org/10.1161/ATVBAHA.111.232678

    Article  CAS  PubMed  Google Scholar 

  49. Burd CE, Jeck WR, Liu Y, Sanoff HK, Wang Z, Sharpless NE (2010) Expression of linear and novel circular forms of an INK4/ARF-associated non-coding RNA correlates with atherosclerosis risk. PLoS Genet 6:e1001233. https://doi.org/10.1371/journal.pgen.1001233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Zhang S, Song G, Yuan J, Qiao S, Xu S, Si Z, Yang Y, Xu X, Wang A (2020) Circular RNA circ_0003204 inhibits proliferation, migration and tube formation of endothelial cell in atherosclerosis via miR-370-3p/TGFbetaR2/phosph-SMAD3 axis. J Biomed Sci 27:11. https://doi.org/10.1186/s12929-019-0595-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Wei MY, Lv RR, Teng Z (2020) Circular RNA circHIPK3 as a novel circRNA regulator of autophagy and endothelial cell dysfunction in atherosclerosis. Eur Rev Med Pharmacol Sci 24:12849–12858. https://doi.org/10.26355/eurrev_202012_24187

    Article  PubMed  Google Scholar 

  52. Tondera D, Czauderna F, Paulick K, Schwarzer R, Kaufmann J, Santel A (2005) The mitochondrial protein MTP18 contributes to mitochondrial fission in mammalian cells. J Cell Sci 118:3049–3059. https://doi.org/10.1242/jcs.02415

    Article  CAS  PubMed  Google Scholar 

  53. Huang S, Li X, Zheng H, Si X, Li B, Wei G, Li C, Chen Y, Chen Y, Liao W, Liao Y, Bin J (2019) Loss of super-enhancer-regulated circRNA Nfix induces cardiac regeneration after myocardial infarction in adult mice. Circulation 139:2857–2876. https://doi.org/10.1161/CIRCULATIONAHA.118.038361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Garikipati VNS, Verma SK, Cheng Z, Liang D, Truongcao MM, Cimini M, Yue Y, Huang G, Wang C, Benedict C, Tang Y, Mallaredy V, Ibetti J, Grisanti L, Schumacher SM, Gao E, Rajan S, Wilusz JE, Goukassian D, Houser SR, Koch WJ, Kishore R (2019) Circular RNA CircFndc3b modulates cardiac repair after myocardial infarction via FUS/VEGF-A axis. Nat Commun 10:4317. https://doi.org/10.1038/s41467-019-11777-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Ni H, Li W, Zhuge Y, Xu S, Wang Y, Chen Y, Shen G, Wang F (2019) Inhibition of circHIPK3 prevents angiotensin II-induced cardiac fibrosis by sponging miR-29b-3p. Int J Cardiol 292:188–196. https://doi.org/10.1016/j.ijcard.2019.04.006

    Article  PubMed  Google Scholar 

  56. Deng Y-Y, Zhang W, She J, Zhang L, Chen T, Zhou J, Yuan Z (2016) GW27-e1167 circular RNA related to PPARγ function as ceRNA of microRNA in human acute myocardial infarction. J Am Coll Cardiol 68:C51–C52. https://doi.org/10.1016/j.jacc.2016.07.189

    Article  Google Scholar 

  57. Cai L, Qi B, Wu X, Peng S, Zhou G, Wei Y, Xu J, Chen S, Liu S (2019) Circular RNA Ttc3 regulates cardiac function after myocardial infarction by sponging miR-15b. J Mol Cell Cardiol 130:10–22. https://doi.org/10.1016/j.yjmcc.2019.03.007

    Article  CAS  PubMed  Google Scholar 

  58. Gupta SK, Garg A, Bar C, Chatterjee S, Foinquinos A, Milting H, Streckfuss-Bomeke K, Fiedler J, Thum T (2018) Quaking inhibits doxorubicin-mediated cardiotoxicity through regulation of cardiac circular RNA expression. Circ Res 122:246–254. https://doi.org/10.1161/CIRCRESAHA.117.311335

    Article  CAS  PubMed  Google Scholar 

  59. Torrealba N, Aranguiz P, Alonso C, Rothermel BA, Lavandero S (2017) Mitochondria in structural and functional cardiac remodeling. Adv Exp Med Biol 982:277–306. https://doi.org/10.1007/978-3-319-55330-6_15

    Article  CAS  PubMed  Google Scholar 

  60. Salgado-Somoza A, Zhang L, Vausort M, Devaux Y (2017) The circular RNA MICRA for risk stratification after myocardial infarction. Int J Cardiol Heart Vasc 17:33–36. https://doi.org/10.1016/j.ijcha.2017.11.001

    Article  PubMed  PubMed Central  Google Scholar 

  61. Zou M, Huang C, Li X, He X, Chen Y, Liao W, Liao Y, Sun J, Liu Z, Zhong L, Bin J (2017) Circular RNA expression profile and potential function of hsa_circRNA_101238 in human thoracic aortic dissection. Oncotarget 8:81825–81837. https://doi.org/10.18632/oncotarget.18998

    Article  PubMed  PubMed Central  Google Scholar 

  62. Geng HH, Li R, Su YM, Xiao J, Pan M, Cai XX, Ji XP (2016) The circular RNA Cdr1as promotes myocardial infarction by mediating the regulation of miR-7a on its target genes expression. PLoS ONE 11:e0151753. https://doi.org/10.1371/journal.pone.0151753

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Zhou LY, Zhai M, Huang Y, Xu S, An T, Wang YH, Zhang RC, Liu CY, Dong YH, Wang M, Qian LL, Ponnusamy M, Zhang YH, Zhang J, Wang K (2019) The circular RNA ACR attenuates myocardial ischemia/reperfusion injury by suppressing autophagy via modulation of the Pink1/ FAM65B pathway. Cell Death Differ 26:1299–1315. https://doi.org/10.1038/s41418-018-0206-4

    Article  CAS  PubMed  Google Scholar 

  64. Wang K, Gan TY, Li N, Liu CY, Zhou LY, Gao JN, Chen C, Yan KW, Ponnusamy M, Zhang YH, Li PF (2017) Circular RNA mediates cardiomyocyte death via miRNA-dependent upregulation of MTP18 expression. Cell Death Differ 24:1111–1120. https://doi.org/10.1038/cdd.2017.61

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Zhou B, Yu JW (2017) A novel identified circular RNA, circRNA_010567, promotes myocardial fibrosis via suppressing miR-141 by targeting TGF-beta1. Biochem Biophys Res Commun 487:769–775. https://doi.org/10.1016/j.bbrc.2017.04.044

    Article  CAS  PubMed  Google Scholar 

  66. Kurz DJ, Decary S, Hong Y, Erusalimsky JD (2000) Senescence-associated (beta)-galactosidase reflects an increase in lysosomal mass during replicative ageing of human endothelial cells. J Cell Sci 113(Pt 20):3613–3622

    Article  CAS  PubMed  Google Scholar 

  67. Du WW, Yang W, Chen Y, Wu ZK, Foster FS, Yang Z, Li X, Yang BB (2017) Foxo3 circular RNA promotes cardiac senescence by modulating multiple factors associated with stress and senescence responses. Eur Heart J 38:1402–1412. https://doi.org/10.1093/eurheartj/ehw001

    Article  CAS  PubMed  Google Scholar 

  68. Nihei T, Takahashi J, Hao K, Kikuchi Y, Odaka Y, Tsuburaya R, Nishimiya K, Matsumoto Y, Ito K, Miyata S, Sakata Y, Shimokawa H (2018) Prognostic impacts of Rho-kinase activity in circulating leucocytes in patients with vasospastic angina. Eur Heart J 39:952–959. https://doi.org/10.1093/eurheartj/ehx657

    Article  CAS  PubMed  Google Scholar 

  69. Enroth S, Johansson A, Enroth SB, Gyllensten U (2014) Strong effects of genetic and lifestyle factors on biomarker variation and use of personalized cutoffs. Nat Commun 5:4684. https://doi.org/10.1038/ncomms5684

    Article  CAS  PubMed  Google Scholar 

  70. Shen L, Hu Y, Lou J, Yin S, Wang W, Wang Y, Xia Y, Wu W (2019) CircRNA0044073 is upregulated in atherosclerosis and increases the proliferation and invasion of cells by targeting miR107. Mol Med Rep 19:3923–3932. https://doi.org/10.3892/mmr.2019.10011

    Article  CAS  PubMed  Google Scholar 

  71. Zhu Y, Pan W, Yang T, Meng X, Jiang Z, Tao L, Wang L (2019) Upregulation of circular RNA CircNFIB Attenuates cardiac fibrosis by sponging miR-433. Front Genet 10:564. https://doi.org/10.3389/fgene.2019.00564

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Siede D, Rapti K, Gorska AA, Katus HA, Altmuller J, Boeckel JN, Meder B, Maack C, Volkers M, Muller OJ, Backs J, Dieterich C (2017) Identification of circular RNAs with host gene-independent expression in human model systems for cardiac differentiation and disease. J Mol Cell Cardiol 109:48–56. https://doi.org/10.1016/j.yjmcc.2017.06.015

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by the National Natural Science Foundation of China (82070314), (81770275), the Key Research and Development Project of Shandong Province (2017GSF18127), and the Taishan Scholar Program of Shandong Province;

Author information

Authors and Affiliations

  1. Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, No. 38 Dengzhou Road, Qingdao, 266071, Shandong, China

    Jie Ju, Xin-zhe Chen, Tao Wang, Cui-yun Liu & Kun Wang

  2. Medical College of Qingdao University, Qingdao, 266021, China

    Ya-nan Song

Authors
  1. Jie Ju
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ya-nan Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xin-zhe Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tao Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Cui-yun Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

WK put forward the theme of circRNA and CVDs. JJ and LC developed the scope of the review. SY, WT and CX carried out the PubMed searches. JJ summarized the relevant papers, accomplished the figures and wrote the manuscript. WK compiled and approved the final version of the manuscript.

Corresponding author

Correspondence to Kun Wang.

Ethics declarations

Conflict of interest

The authors declare that there is no conflict of interests regarding the publication of this article.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ju, J., Song, Yn., Chen, Xz. et al. circRNA is a potential target for cardiovascular diseases treatment. Mol Cell Biochem 477, 417–430 (2022). https://doi.org/10.1007/s11010-021-04286-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-021-04286-z

Keywords

Search

Navigation