Skip to main content
SpringerLink
Log in

Noncoding RNAs in Cardiac Hypertrophy

  • Review
  • Published:
Journal of Cardiovascular Translational Research Aims and scope Submit manuscript

Abstract

Cardiac hypertrophy is classified as pathological and physiological hypertrophy. Pathological hypertrophy typically precedes the onset of heart failure, one of the largest contributors to disease burden and deaths worldwide. In contrast, physiological hypertrophy is an adaptive response and protects against adverse cardiac remodeling. Noncoding RNAs (ncRNAs) have drawn significant attention over the last couple of decades, and their dysregulation is increasingly being linked to cardiac hypertrophy and cardiovascular diseases. In this review, we will summarize the profiling, function, and molecular mechanism of microRNAs, long noncoding RNAs, and circular RNAs in pathological cardiac hypertrophy. Additionally, we also review microRNAs responsible for physiological hypertrophy. With better understanding of ncRNAs in cardiac hypertrophy, manipulation of the important ncRNAs will offer exciting avenues for the prevention and therapy of heart failure.

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.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Iismaa, S. E., & Graham, R. M. (2003). Dissecting cardiac hypertrophy and signaling pathways: evidence for an interaction between multifunctional g proteins and prostanoids. Circulation Research, 92(10), 1059–1061.

    CAS  PubMed  Google Scholar 

  2. Shimizu, I., & Minamino, T. (2016). Physiological and pathological cardiac hypertrophy. Journal of Molecular and Cellular Cardiology, 97, 245–262.

    CAS  PubMed  Google Scholar 

  3. Frey, N., & Olson, E. N. (2003). Cardiac hypertrophy: the good, the bad, and the ugly. Annual Review of Physiology, 65, 45–79.

    CAS  PubMed  Google Scholar 

  4. Bagga, S., Bracht, J., Hunter, S., Massirer, K., Holtz, J., Eachus, R., et al. (2005). Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation. Cell, 122(4), 553–563.

    CAS  PubMed  Google Scholar 

  5. Olsen, P. H., & Ambros, V. (1999). The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Developmental Biology, 216(2), 671–680.

    CAS  PubMed  Google Scholar 

  6. Guo, H., Ingolia, N. T., Weissman, J. S., & Bartel, D. P. (2010). Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature, 466(7308), 835–840.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Bronze-da-Rocha, E. (2014, 2014). MicroRNAs expression profiles in cardiovascular diseases. Biomed Res Int, 985408.

  8. Chen, L. J., Xu, R., Yu, H. M., Chang, Q., & Zhong, J. C. (2015). The ACE2/Apelin signaling, microRNAs, and hypertension. International Journal of Hypertension, 2015, 896861.

    PubMed  PubMed Central  Google Scholar 

  9. Pang, K. C., Frith, M. C., & Mattick, J. S. (2006). Rapid evolution of noncoding RNAs: lack of conservation does not mean lack of function. Trends in Genetics, 22(1), 1–5.

    CAS  PubMed  Google Scholar 

  10. Devaux, Y., Zangrando, J., Schroen, B., Creemers, E. E., Pedrazzini, T., Chang, C. P., et al. (2015). Long noncoding RNAs in cardiac development and ageing. Nature Reviews. Cardiology, 12(7), 415–425.

    CAS  PubMed  Google Scholar 

  11. Hansen, T. B., Jensen, T. I., Clausen, B. H., Bramsen, J. B., Finsen, B., Damgaard, C. K., et al. (2013). Natural RNA circles function as efficient microRNA sponges. Nature, 495(7441), 384–388.

    CAS  PubMed  Google Scholar 

  12. Lasda, E., & Parker, R. (2014). Circular RNAs: diversity of form and function. RNA, 20(12), 1829–1842.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Jeck, W. R., Sorrentino, J. A., Wang, K., Slevin, M. K., Burd, C. E., Liu, J., et al. (2013). Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA, 19(2), 141–157.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Zhang, X. O., Wang, H. B., Zhang, Y., Lu, X., Chen, L. L., & Yang, L. (2014). Complementary sequence-mediated exon circularization. Cell, 159(1), 134–147.

    CAS  PubMed  Google Scholar 

  15. Ashwal-Fluss, R., Meyer, M., Pamudurti, N. R., Ivanov, A., Bartok, O., Hanan, M., et al. (2014). circRNA biogenesis competes with pre-mRNA splicing. Molecular Cell, 56(1), 55–66.

    CAS  PubMed  Google Scholar 

  16. Zhang, Y., Zhang, X. O., Chen, T., Xiang, J. F., Yin, Q. F., Xing, Y. H., et al. (2013). Circular intronic long noncoding RNAs. Molecular Cell, 51(6), 792–806.

    CAS  PubMed  Google Scholar 

  17. Memczak, S., Jens, M., Elefsinioti, A., Torti, F., Krueger, J., Rybak, A., et al. (2013). Circular RNAs are a large class of animal RNAs with regulatory potency. Nature, 495(7441), 333–338.

    CAS  Google Scholar 

  18. Kapusta, A., & Feschotte, C. (2014). Volatile evolution of long noncoding RNA repertoires: mechanisms and biological implications. Trends in Genetics, 30(10), 439–452.

    CAS  PubMed  Google Scholar 

  19. Ounzain, S., Micheletti, R., Beckmann, T., Schroen, B., Alexanian, M., Pezzuto, I., et al. (2015). Genome-wide profiling of the cardiac transcriptome after myocardial infarction identifies novel heart-specific long non-coding RNAs. European Heart Journal, 36(6), 353–368a.

    CAS  PubMed  Google Scholar 

  20. Zhao, Y., Li, H., Fang, S., Kang, Y., Wu, W., Hao, Y., et al. (2016). NONCODE 2016: an informative and valuable data source of long non-coding RNAs. Nucleic Acids Research, 44(D1), D203–D208.

    CAS  PubMed  Google Scholar 

  21. Sun, L., Zhang, Y., Zhang, Y., Gu, Y., Xuan, L., Liu, S., et al. (2014). Expression profile of long non-coding RNAs in a mouse model of cardiac hypertrophy. International Journal of Cardiology, 177(1), 73–75.

    PubMed  Google Scholar 

  22. Li, X., Zhang, L., & Liang, J. (2016). Unraveling the expression profiles of long noncoding RNAs in rat cardiac hypertrophy and functions of lncRNA BC088254 in cardiac hypertrophy induced by transverse aortic constriction. Cardiology, 134(2), 84–98.

    CAS  PubMed  Google Scholar 

  23. Yang, K. C., Yamada, K. A., Patel, A. Y., Topkara, V. K., George, I., Cheema, F. H., et al. (2014). Deep RNA sequencing reveals dynamic regulation of myocardial noncoding RNAs in failing human heart and remodeling with mechanical circulatory support. Circulation, 129(9), 1009–1021.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Schiano, C., Costa, V., Aprile, M., Grimaldi, V., Maiello, C., Esposito, R., et al. (2017). Heart failure: pilot transcriptomic analysis of cardiac tissue by RNA-sequencing. Cardiol J.

  25. Zhang, J., Feng, C., Song, C., Ai, B., Bai, X., Liu, Y., et al. (2018). Identification and analysis of a key long non-coding RNAs (lncRNAs)-associated module reveal functional lncRNAs in cardiac hypertrophy. Journal of Cellular and Molecular Medicine, 22(2), 892–903.

    CAS  PubMed  Google Scholar 

  26. Wang, K., Liu, F., Zhou, L. Y., Long, B., Yuan, S. M., Wang, Y., et al. (2014). The long noncoding RNA CHRF regulates cardiac hypertrophy by targeting miR-489. Circulation Research, 114(9), 1377–1388.

    CAS  PubMed  Google Scholar 

  27. Zhu, X. H., Yuan, Y. X., Rao, S. L., & Wang, P. (2016). LncRNA MIAT enhances cardiac hypertrophy partly through sponging miR-150. European Review for Medical and Pharmacological Sciences, 20(17), 3653–3660.

    PubMed  Google Scholar 

  28. Lai, Y. J., He, S., Ma, L. M., Lin, H., Ren, B. Y., Ma, J., et al. (2017). HOTAIR functions as a competing endogenous RNA to regulate PTEN expression by inhibiting miR-19 in cardiac hypertrophy. Molecular and Cellular Biochemistry, 432(1–2), 179–187.

    CAS  PubMed  Google Scholar 

  29. Jiang, F., Zhou, X., & Huang, J. (2016). Long non-coding RNA-ROR mediates the reprogramming in cardiac hypertrophy. PLoS One, 11(4), e0152767.

    PubMed  PubMed Central  Google Scholar 

  30. Keniry, A., Oxley, D., Monnier, P., Kyba, M., Dandolo, L., Smits, G., et al. (2012). The H19 lincRNA is a developmental reservoir of miR-675 that suppresses growth and lgf1r. Nature Cell Biology, 14(7), 659–665.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Liu, L. T., An, X. B., Li, Z. H., Song, Y., Li, L. L., Zuo, S., et al. (2016). The H19 long noncoding RNA is a novel negative regulator of cardiomyocyte hypertrophy. Cardiovascular Research, 111(1), 56–65.

    CAS  PubMed  Google Scholar 

  32. Han, P., Li, W., Lin, C. H., Yang, J., Shang, C., Nuernberg, S. T., et al. (2014). A long noncoding RNA protects the heart from pathological hypertrophy. Nature, 514(7520), 102–106.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Wang, Z., Zhang, X. J., Ji, Y. X., Zhang, P., Deng, K. Q., Gong, J., et al. (2016). The long noncoding RNA Chaer defines an epigenetic checkpoint in cardiac hypertrophy. Nature Medicine, 22(10), 1131–1139.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Shao, M., Chen, G., Lv, F., Liu, Y., Tian, H., Tao, R., et al. (2017). LncRNA TINCR attenuates cardiac hypertrophy by epigenetically silencing CaMKII. Oncotarget, 8(29), 47565–47573.

    PubMed  PubMed Central  Google Scholar 

  35. Viereck, J., Kumarswamy, R., Foinquinos, A., Xiao, K., Avramopoulos, P., Kunz, M., et al. (2016). Long noncoding RNA Chast promotes cardiac remodeling. Science Translational Medicine, 8(326), 326ra322.

    Google Scholar 

  36. Sun, W., Julie Li, Y. S., Huang, H. D., Shyy, J. Y., & Chien, S. (2010). MicroRNA: a master regulator of cellular processes for bioengineering systems. Annual Review of Biomedical Engineering, 12, 1–27.

    CAS  PubMed  Google Scholar 

  37. Zhao, Y., Ransom, J. F., Li, A., Vedantham, V., von Drehle, M., Muth, A. N., et al. (2007). Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2. Cell, 129(2), 303–317.

    CAS  PubMed  Google Scholar 

  38. Zhao, Y., Samal, E., & Srivastava, D. (2005). Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis. Nature, 436(7048), 214–220.

    CAS  PubMed  Google Scholar 

  39. Chen, J. F., Mandel, E. M., Thomson, J. M., Wu, Q., Callis, T. E., Hammond, S. M., et al. (2006). The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nature Genetics, 38(2), 228–233.

    CAS  PubMed  Google Scholar 

  40. Yang, B., Lin, H., Xiao, J., Lu, Y., Luo, X., Li, B., et al. (2007). The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2. Nature Medicine, 13(4), 486–491.

    CAS  PubMed  Google Scholar 

  41. Sayed, D., Hong, C., Chen, I. Y., Lypowy, J., & Abdellatif, M. (2007). MicroRNAs play an essential role in the development of cardiac hypertrophy. Circulation Research, 100(3), 416–424.

    CAS  PubMed  Google Scholar 

  42. Ikeda, S., He, A., Kong, S. W., Lu, J., Bejar, R., Bodyak, N., et al. (2009). MicroRNA-1 negatively regulates expression of the hypertrophy-associated calmodulin and Mef2a genes. Molecular and Cellular Biology, 29(8), 2193–2204.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Elia, L., Contu, R., Quintavalle, M., Varrone, F., Chimenti, C., Russo, M. A., et al. (2009). Reciprocal regulation of microRNA-1 and insulin-like growth factor-1 signal transduction cascade in cardiac and skeletal muscle in physiological and pathological conditions. Circulation, 120(23), 2377–2385.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Li, Q., Song, X. W., Zou, J., Wang, G. K., Kremneva, E., Li, X. Q., et al. (2010). Attenuation of microRNA-1 derepresses the cytoskeleton regulatory protein twinfilin-1 to provoke cardiac hypertrophy. Journal of Cell Science, 123(Pt 14), 2444–2452.

    CAS  PubMed  Google Scholar 

  45. Yuan, W., Tang, C., Zhu, W., Zhu, J., Lin, Q., Fu, Y., et al. (2016). CDK6 mediates the effect of attenuation of miR-1 on provoking cardiomyocyte hypertrophy. Molecular and Cellular Biochemistry, 412(1–2), 289–296.

    CAS  PubMed  Google Scholar 

  46. Karakikes, I., Chaanine, A. H., Kang, S., Mukete, B. N., Jeong, D., Zhang, S., et al. (2013). Therapeutic cardiac-targeted delivery of miR-1 reverses pressure overload-induced cardiac hypertrophy and attenuates pathological remodeling. Journal of the American Heart Association, 2(2), e000078.

    PubMed  PubMed Central  Google Scholar 

  47. Liu, N., Williams, A. H., Kim, Y., McAnally, J., Bezprozvannaya, S., Sutherland, L. B., et al. (2007). An intragenic MEF2-dependent enhancer directs muscle-specific expression of microRNAs 1 and 133. Proceedings of the National Academy of Sciences of the United States of America, 104(52), 20844–20849.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. McCarthy, J. J. (2008). MicroRNA-206: the skeletal muscle-specific myomiR. Biochimica et Biophysica Acta, 1779(11), 682–691.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Care, A., Catalucci, D., Felicetti, F., Bonci, D., Addario, A., Gallo, P., et al. (2007). MicroRNA-133 controls cardiac hypertrophy. Nature Medicine, 13(5), 613–618.

    CAS  PubMed  Google Scholar 

  50. Liu, N., Bezprozvannaya, S., Williams, A. H., Qi, X., Richardson, J. A., Bassel-Duby, R., et al. (2008). microRNA-133a regulates cardiomyocyte proliferation and suppresses smooth muscle gene expression in the heart. Genes & Development, 22(23), 3242–3254.

    CAS  Google Scholar 

  51. Luo, X., Lin, H., Pan, Z., Xiao, J., Zhang, Y., Lu, Y., et al. (2008). Down-regulation of miR-1/miR-133 contributes to re-expression of pacemaker channel genes HCN2 and HCN4 in hypertrophic heart. The Journal of Biological Chemistry, 283(29), 20045–20052.

    CAS  PubMed  Google Scholar 

  52. Dong, D. L., Chen, C., Huo, R., Wang, N., Li, Z., Tu, Y. J., et al. (2010). Reciprocal repression between microRNA-133 and calcineurin regulates cardiac hypertrophy: a novel mechanism for progressive cardiac hypertrophy. Hypertension, 55(4), 946–952.

    CAS  PubMed  Google Scholar 

  53. Li, Q., Lin, X., Yang, X., & Chang, J. (2010). NFATc4 is negatively regulated in miR-133a-mediated cardiomyocyte hypertrophic repression. American Journal of Physiology. Heart and Circulatory Physiology, 298(5), H1340–H1347.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Han, M., Yang, Z., Sayed, D., He, M., Gao, S., Lin, L., et al. (2012). GATA4 expression is primarily regulated via a miR-26b-dependent post-transcriptional mechanism during cardiac hypertrophy. Cardiovascular Research, 93(4), 645–654.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Li, R., Yan, G., Zhang, Q., Jiang, Y., Sun, H., Hu, Y., et al. (2013). miR-145 inhibits isoproterenol-induced cardiomyocyte hypertrophy by targeting the expression and localization of GATA6. FEBS Letters, 587(12), 1754–1761.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Ganesan, J., Ramanujam, D., Sassi, Y., Ahles, A., Jentzsch, C., Werfel, S., et al. (2013). MiR-378 controls cardiac hypertrophy by combined repression of mitogen-activated protein kinase pathway factors. Circulation, 127(21), 2097–2106.

    CAS  PubMed  Google Scholar 

  57. Wang, Y. S., Zhou, J., Hong, K., Cheng, X. S., & Li, Y. G. (2015). MicroRNA-223 displays a protective role against cardiomyocyte hypertrophy by targeting cardiac troponin I-interacting kinase. Cellular Physiology and Biochemistry, 35(4), 1546–1556.

    CAS  PubMed  Google Scholar 

  58. Lee, J. S., Yang, D. K., Park, J. H., Kim, J. O., Park, W. J., Cho, C., et al. (2017). MicroRNA-101b attenuates cardiomyocyte hypertrophy by inhibiting protein kinase C epsilon signaling. FEBS Letters, 591(1), 16–27.

    CAS  PubMed  Google Scholar 

  59. Duan, Q., Chen, C., Yang, L., Li, N., Gong, W., Li, S., et al. (2015). MicroRNA regulation of unfolded protein response transcription factor XBP1 in the progression of cardiac hypertrophy and heart failure in vivo. Journal of Translational Medicine, 13, 363.

    PubMed  PubMed Central  Google Scholar 

  60. Yang, Y., Ago, T., Zhai, P., Abdellatif, M., & Sadoshima, J. (2011). Thioredoxin 1 negatively regulates angiotensin II-induced cardiac hypertrophy through upregulation of miR-98/let-7. Circulation Research, 108(3), 305–313.

    CAS  PubMed  Google Scholar 

  61. Huang, J., Sun, W., Huang, H., Ye, J., Pan, W., Zhong, Y., et al. (2014). miR-34a modulates angiotensin II-induced myocardial hypertrophy by direct inhibition of ATG9A expression and autophagic activity. PLoS One, 9(4), e94382.

    PubMed  PubMed Central  Google Scholar 

  62. Pan, W., Zhong, Y., Cheng, C., Liu, B., Wang, L., Li, A., et al. (2013). MiR-30-regulated autophagy mediates angiotensin II-induced myocardial hypertrophy. PLoS One, 8(1), e53950.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Yan, M., Chen, C., Gong, W., Yin, Z., Zhou, L., Chaugai, S., et al. (2015). miR-21-3p regulates cardiac hypertrophic response by targeting histone deacetylase-8. Cardiovascular Research, 105(3), 340–352.

    CAS  PubMed  Google Scholar 

  64. Wang, K., Long, B., Zhou, J., & Li, P. F. (2010). miR-9 and NFATc3 regulate myocardin in cardiac hypertrophy. The Journal of Biological Chemistry, 285(16), 11903–11912.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Kim, J. O., Song, D. W., Kwon, E. J., Hong, S. E., Song, H. K., Min, C. K., et al. (2015). miR-185 plays an anti-hypertrophic role in the heart via multiple targets in the calcium-signaling pathways. PLoS One, 10(3), e0122509.

    PubMed  PubMed Central  Google Scholar 

  66. van Rooij, E., Sutherland, L. B., Liu, N., Williams, A. H., McAnally, J., Gerard, R. D., et al. (2006). A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure. Proceedings of the National Academy of Sciences of the United States of America, 103(48), 18255–18260.

    PubMed  PubMed Central  Google Scholar 

  67. Zhang, X., Ji, R., Liao, X., Castillero, E., Kennel, P. J., Brunjes, D. L., et al. (2018). miR-195 regulates metabolism in failing myocardium via alterations in SIRT3 expression and mitochondrial protein acetylation. Circulation. https://doi.org/10.1161/CIRCULATIONAHA.117.030486.

  68. Callis, T. E., Pandya, K., Seok, H. Y., Tang, R. H., Tatsuguchi, M., Huang, Z. P., et al. (2009). MicroRNA-208a is a regulator of cardiac hypertrophy and conduction in mice. The Journal of Clinical Investigation, 119(9), 2772–2786.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Bernardo, B. C., Gao, X. M., Winbanks, C. E., Boey, E. J., Tham, Y. K., Kiriazis, H., et al. (2012). Therapeutic inhibition of the miR-34 family attenuates pathological cardiac remodeling and improves heart function. Proceedings of the National Academy of Sciences of the United States of America, 109(43), 17615–17620.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Bang, C., Batkai, S., Dangwal, S., Gupta, S. K., Foinquinos, A., Holzmann, A., et al. (2014). Cardiac fibroblast-derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy. The Journal of Clinical Investigation, 124(5), 2136–2146.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. da Costa Martins, P. A., Salic, K., Gladka, M. M., Armand, A. S., Leptidis, S., el Azzouzi, H., et al. (2010). MicroRNA-199b targets the nuclear kinase Dyrk1a in an auto-amplification loop promoting calcineurin/NFAT signalling. Nature Cell Biology, 12(12), 1220–1227.

    PubMed  Google Scholar 

  72. Wang, J., Song, Y., Zhang, Y., Xiao, H., Sun, Q., Hou, N., et al. (2012). Cardiomyocyte overexpression of miR-27b induces cardiac hypertrophy and dysfunction in mice. Cell Research, 22(3), 516–527.

    CAS  PubMed  Google Scholar 

  73. Wang, K., Lin, Z. Q., Long, B., Li, J. H., Zhou, J., & Li, P. F. (2012). Cardiac hypertrophy is positively regulated by microRNA miR-23a. The Journal of Biological Chemistry, 287(1), 589–599.

    CAS  PubMed  Google Scholar 

  74. Yang, J., Nie, Y., Wang, F., Hou, J., Cong, X., Hu, S., et al. (2013). Reciprocal regulation of miR-23a and lysophosphatidic acid receptor signaling in cardiomyocyte hypertrophy. Biochimica et Biophysica Acta, 1831(8), 1386–1394.

    CAS  PubMed  Google Scholar 

  75. Ucar, A., Gupta, S. K., Fiedler, J., Erikci, E., Kardasinski, M., Batkai, S., et al. (2012). The miRNA-212/132 family regulates both cardiac hypertrophy and cardiomyocyte autophagy. Nature Communications, 3, 1078.

    PubMed  PubMed Central  Google Scholar 

  76. Wang, C., Wang, S., Zhao, P., Wang, X., Wang, J., Wang, Y., et al. (2012). MiR-221 promotes cardiac hypertrophy in vitro through the modulation of p27 expression. Journal of Cellular Biochemistry, 113(6), 2040–2046.

    CAS  PubMed  Google Scholar 

  77. Ge, Y., Pan, S., Guan, D., Yin, H., Fan, Y., Liu, J., et al. (2013). MicroRNA-350 induces pathological heart hypertrophy by repressing both p38 and JNK pathways. Biochimica et Biophysica Acta, 1832(1), 1–10.

    CAS  PubMed  Google Scholar 

  78. Huang, Z. P., Chen, J., Seok, H. Y., Zhang, Z., Kataoka, M., Hu, X., et al. (2013). MicroRNA-22 regulates cardiac hypertrophy and remodeling in response to stress. Circulation Research, 112(9), 1234–1243.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Li, C., Li, X., Gao, X., Zhang, R., Zhang, Y., Liang, H., et al. (2014). MicroRNA-328 as a regulator of cardiac hypertrophy. International Journal of Cardiology, 173(2), 268–276.

    PubMed  Google Scholar 

  80. He, W., Huang, H., Xie, Q., Wang, Z., Fan, Y., Kong, B., et al. (2016). MiR-155 knockout in fibroblasts improves cardiac remodeling by targeting tumor protein p53-inducible nuclear protein 1. Journal of Cardiovascular Pharmacology and Therapeutics, 21(4), 423–435.

    CAS  PubMed  Google Scholar 

  81. Sanger, H. L., Klotz, G., Riesner, D., Gross, H. J., & Kleinschmidt, A. K. (1976). Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures. Proceedings of the National Academy of Sciences of the United States of America, 73(11), 3852–3856.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Szabo, L., & Salzman, J. (2016). Detecting circular RNAs: bioinformatic and experimental challenges. Nature Reviews. Genetics, 17(11), 679–692.

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Qu, S., Zhong, Y., Shang, R., Zhang, X., Song, W., Kjems, J., et al. (2016). The emerging landscape of circular RNA in life processes. RNA Biol, 1–8.

  84. Zheng, Q., Bao, C., Guo, W., Li, S., Chen, J., Chen, B., et al. (2016). Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs. Nature Communications, 7, 11215.

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Wang, K., Long, B., Liu, F., Wang, J. X., Liu, C. Y., Zhao, B., et al. (2016). A circular RNA protects the heart from pathological hypertrophy and heart failure by targeting miR-223. European Heart Journal, 37(33), 2602–2611.

    CAS  PubMed  Google Scholar 

  86. Jakobi, T., Czaja-Hasse, L. F., Reinhardt, R., & Dieterich, C. (2016). Profiling and validation of the circular RNA repertoire in adult murine hearts. Genomics, Proteomics & Bioinformatics, 14(4), 216–223.

    Google Scholar 

  87. Khan, M. A., Reckman, Y. J., Aufiero, S., van den Hoogenhof, M. M., van der Made, I., Beqqali, A., et al. (2016). RBM20 regulates circular RNA production from the Titin gene. Circulation Research, 119(9), 996–1003.

    CAS  PubMed  Google Scholar 

  88. Werfel, S., Nothjunge, S., Schwarzmayr, T., Strom, T. M., Meitinger, T., & Engelhardt, S. (2016). Characterization of circular RNAs in human, mouse and rat hearts. Journal of Molecular and Cellular Cardiology, 98, 103–107.

    CAS  PubMed  Google Scholar 

  89. Tan, W. L., Lim, B. T., Anene-Nzelu, C. G., Ackers-Johnson, M., Dashi, A., See, K., et al. (2017). A landscape of circular RNA expression in the human heart. Cardiovascular Research, 113(3), 298–309.

    CAS  PubMed  Google Scholar 

  90. Fernandes, T., Hashimoto, N. Y., Magalhaes, F. C., Fernandes, F. B., Casarini, D. E., Carmona, A. K., et al. (2011). Aerobic exercise training-induced left ventricular hypertrophy involves regulatory microRNAs, decreased angiotensin-converting enzyme-angiotensin II, and synergistic regulation of angiotensin-converting enzyme 2-angiotensin (1-7). Hypertension, 58(2), 182–189.

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Ramasamy, S., Velmurugan, G., Shanmugha Rajan, K., Ramprasath, T., & Kalpana, K. (2015). MiRNAs with apoptosis regulating potential are differentially expressed in chronic exercise-induced physiologically hypertrophied hearts. PLoS One, 10(3), e0121401.

    PubMed  PubMed Central  Google Scholar 

  92. Ma, Z., Qi, J., Meng, S., Wen, B., & Zhang, J. (2013). Swimming exercise training-induced left ventricular hypertrophy involves microRNAs and synergistic regulation of the PI3K/AKT/mTOR signaling pathway. European Journal of Applied Physiology, 113(10), 2473–2486.

    CAS  PubMed  Google Scholar 

  93. Soci, U. P., Fernandes, T., Hashimoto, N. Y., Mota, G. F., Amadeu, M. A., Rosa, K. T., et al. (2011). MicroRNAs 29 are involved in the improvement of ventricular compliance promoted by aerobic exercise training in rats. Physiological Genomics, 43(11), 665–673.

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Martinelli, N. C., Cohen, C. R., Santos, K. G., Castro, M. A., Biolo, A., Frick, L., et al. (2014). An analysis of the global expression of microRNAs in an experimental model of physiological left ventricular hypertrophy. PLoS One, 9(4), e93271.

    PubMed  PubMed Central  Google Scholar 

  95. Liu, X., Xiao, J., Zhu, H., Wei, X., Platt, C., Damilano, F., et al. (2015). miR-222 is necessary for exercise-induced cardiac growth and protects against pathological cardiac remodeling. Cell Metabolism, 21(4), 584–595.

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Shi, J., Bei, Y., Kong, X., Liu, X., Lei, Z., Xu, T., et al. (2017). miR-17-3p contributes to exercise-induced cardiac growth and protects against myocardial ischemia-reperfusion injury. Theranostics, 7(3), 664–676.

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Li, Z., Liu, L., Hou, N., Song, Y., An, X., Zhang, Y., et al. (2016). miR-199-sponge transgenic mice develop physiological cardiac hypertrophy. Cardiovascular Research, 110(2), 258–267.

    CAS  PubMed  Google Scholar 

  98. Yang, L., Li, Y., Wang, X., Mu, X., Qin, D., Huang, W., et al. (2016). Overexpression of miR-223 tips the balance of pro- and anti-hypertrophic signaling cascades toward physiologic cardiac hypertrophy. The Journal of Biological Chemistry, 291(30), 15700–15713.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This review was supported by the grants from the CAMS Innovation Fund for Medical Sciences (CIFMS, 2016-12M-1-006), National Natural Science Foundation of China (81400647 to Y Bei).

Author information

Author notes

  1. Yongqin Li and Yajun Liang contributed equally to this work.

Authors and Affiliations

  1. Cardiac Regeneration and Ageing Lab, School of Life Science, Shanghai University, 333 Nan Chen Road, Shanghai, 200444, China

    Yongqin Li, Yajun Liang, Yujiao Zhu & Yihua Bei

  2. State Key Laboratory of Cardiovascular Disease, Heart Failure Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Bei Li Tu Road, Beijing, 100037, China

    Yuhui Zhang

Authors
  1. Yongqin Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yajun Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yujiao Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuhui Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yihua Bei
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yuhui Zhang or Yihua Bei.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflicts of interest.

Additional information

Associate Editor Enrique Lara-Pezzi oversaw the review of this article

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, Y., Liang, Y., Zhu, Y. et al. Noncoding RNAs in Cardiac Hypertrophy. J. of Cardiovasc. Trans. Res. 11, 439–449 (2018). https://doi.org/10.1007/s12265-018-9797-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12265-018-9797-x

Keywords

Search

Navigation