Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

The roles of long noncoding RNA NEAT1 in cardiovascular diseases

Hypertension Research volume 47, pages 735–746 (2024)Cite this article

Abstract

The morbidity of cardiovascular diseases (CVDs) gradually increases worldwide. Long noncoding RNAs (lncRNAs) are a large class of non-(protein)-coding RNAs with lengths beyond 200 nucleotides. Increasing evidence suggests that lncRNA NEAT1 plays important roles in the pathogenesis of CVDs, such as myocardial infarction, heart failure, myocardial ischemia-reperfusion (I/R) injury, atherosclerosis, hypertension, cardiomyopathy, and others. We summarized the current studies of NEAT1 in CVDs, which shed light on the understanding of the molecular mechanisms of CVDs and understanding the therapeutic potential of NEAT1.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Habimana O, Modupe Salami O, Peng J, Yi GH. Therapeutic implications of targeting pyroptosis in cardiac-related etiology of heart failure. Biochem Pharm. 2022;204:115235.

    Article  CAS  PubMed  Google Scholar 

  2. Gonciar D, Mocan T, Agoston-Coldea L. Nanoparticles targeting the molecular pathways of heart remodeling and regeneration. Pharmaceutics. 2022;14:711.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Jiang X, Ning Q. The mechanism of lncRNA H19 in fibrosis and its potential as novel therapeutic target. Mech Ageing Dev. 2020;188:111243.

    Article  CAS  PubMed  Google Scholar 

  4. Jiang X, Ning Q. The mechanisms of lncRNA GAS5 in cardiovascular cells and its potential as novel therapeutic target. J Drug Target. 2020;20:1012–7.

    Article  CAS  Google Scholar 

  5. Lorenzen JM, Thum T. Long noncoding RNAs in kidney and cardiovascular diseases. Nat Rev Nephrol. 2016;12:360–73.

    Article  CAS  PubMed  Google Scholar 

  6. Zhang Y, Jiao L, Sun L, Li Y, Gao Y, Xu C, et al. LncRNA ZFAS1 as a SERCA2a inhibitor to cause intracellular Ca2+ overload and contractile dysfunction in a mouse model of myocardial infarction. Circ Res. 2018;122:1354–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Huang SF, Ye WC. LncRNA MALAT1 facilitated the progression of myocardial infarction by sponging miR-26b. Int J Cardiol. 2021;335:24.

    Article  PubMed  Google Scholar 

  8. Hoepfner J, Leonardy J, Lu D, Schmidt K, Hunkler HJ, Biß S, et al. The long non-coding RNA NRON promotes the development of cardiac hypertrophy in the murine heart. Mol Ther. 2022;30:1265–74.

    Article  CAS  PubMed  Google Scholar 

  9. Tian C, Hu S, Yu J, Li W, Li P, Huang H. CREB1 transcription-activated lncRNA PVT1 promotes cardiac fibrosis via miR-145/HCN1 axis. Int J Cardiol. 2022;353:88–95.

    Article  PubMed  Google Scholar 

  10. Gidlöf O, Bader K, Celik S, Grossi M, Nakagawa S, Hirose T, et al. Inhibition of the long non-coding RNA NEAT1 protects cardiomyocytes from hypoxia in vitro via decreased pri-miRNA processing. Cell Death Dis. 2020;11:677.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Smith NE, Spencer-Merris P, Fox AH, Petersen J, Michael MZ. The long and the short of it: NEAT1 and cancer cell metabolism. Cancers (Basel). 2022;14:4388.

    Article  CAS  PubMed  Google Scholar 

  12. Gu J, Zhang B, An R, Qian W, Han L, Duan W, et al. Molecular interactions of the long noncoding RNA NEAT1 in cancer. Cancers (Basel). 2022;14:4009.

    Article  CAS  PubMed  Google Scholar 

  13. Knutsen E, Harris AL, Perander M. Expression and functions of long non-coding RNA NEAT1 and isoforms in breast cancer. Br J Cancer. 2022;126:551–61.

    Article  CAS  PubMed  Google Scholar 

  14. Pisani G, Baron B. NEAT1 and paraspeckles in cancer development and chemoresistance. Noncoding RNA. 2020;6:43. Oct 30

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Wang Z, Li K, Huang W. Long non‑coding RNA NEAT1‑centric gene regulation. Cell Mol Life Sci. 2020;77:3769–79.

    Article  CAS  PubMed  Google Scholar 

  16. Li K, Wang Z. lncRNA NEAT1: key player in neurodegenerative diseases. Ageing Res Rev. 2023;86:101878.

    Article  CAS  PubMed  Google Scholar 

  17. Wei Q, Zhou HY, Shi XD, Cao HY, Qin L. Long noncoding RNA NEAT1 promotes myocardiocyte apoptosis and suppresses proliferation through regulation of miR-129-5p. J Cardiovasc Pharm. 2019;74:535–41.

    Article  CAS  Google Scholar 

  18. Zhao J, Chen F, Ma W, Zhang P. Suppression of long noncoding RNA NEAT1 attenuates hypoxia-induced cardiomyocytes injury by targeting miR-378a-3p. Gene. 2020;731:144324.

    Article  CAS  PubMed  Google Scholar 

  19. Chen Z, Yan Y, Wu J, Qi C, Liu J, Wang J. Expression level and diagnostic value of exosomal NEAT1/miR-204/MMP-9 in acute ST-segment elevation myocardial infarction. IUBMB Life. 2020;72:2499–507.

    Article  CAS  PubMed  Google Scholar 

  20. Wang L, Wang L, Wang Q. Constitutive activation of the NEAT1/miR-22-3p/Ltb4r1 signaling pathway in mice with myocardial injury following acute myocardial infarction. Aging (Albany NY). 2021;13:15307–19.

    Article  CAS  PubMed  Google Scholar 

  21. Wu Z, Bai Y, Qi Y, Chang C, Jiao Y, Bai Y, et al. lncRNA NEAT1 downregulation ameliorates the myocardial infarction of mice by regulating the miR-582-5p/F2RL2 axis. Cardiovasc Ther. 2022;2022:4481360.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Gast M, Rauch BH, Haghikia A, Nakagawa S, Haas J, Stroux A, et al. Long noncoding RNA NEAT1 modulates immune cell functions and is suppressed in early onset myocardial infarction patients. Cardiovasc Res. 2019;115:1886–906.

    Article  CAS  PubMed  Google Scholar 

  23. Su J, Hu Y, Cheng J, Li Z, Li J, Zheng N, et al. Comprehensive analysis of the RNA transcriptome expression profiles and construction of the ceRNA network in heart failure patients with sacubitril/valsartan therapeutic heterogeneity after acute myocardial infarction. Eur J Pharm. 2023;944:175547.

    Article  CAS  Google Scholar 

  24. Zhang H, Zhang N, Jiang W, Lun X. Clinical significance of the long non-coding RNA NEAT1/miR-129-5p axis in the diagnosis and prognosis for patients with chronic heart failure. Exp Ther Med. 2021;21:512.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Yuan Z, Huang W. New developments in exosomal lncRNAs in cardiovascular diseases. Front Cardiovasc Med. 2021;8:709069.

    Article  Google Scholar 

  26. Ma M, Hui J, Zhang QY, Zhu Y, He Y, Liu XJ. Long non-coding RNA nuclear-enriched abundant transcript 1 inhibition blunts myocardial ischemia reperfusion injury via autophagic flux arrest and apoptosis in streptozotocin-induced diabetic rats. Atherosclerosis. 2018;277:113–22.

    Article  CAS  PubMed  Google Scholar 

  27. Yan H, Liang H, Liu L, Chen D, Zhang Q. Long noncoding RNA NEAT1 sponges miR‑125a‑5p to suppress cardiomyocyte apoptosis via BCL2L12. Mol Med Rep. 2019;19:4468–74.

    CAS  PubMed  Google Scholar 

  28. Du XJ, Wei J, Tian D, Yan C, Hu P, Wu X, et al. NEAT1 promotes myocardial ischemia-reperfusion injury via activating the MAPK signaling pathway. J Cell Physiol. 2019;234:18773–80.

    Article  CAS  PubMed  Google Scholar 

  29. Ren L, Chen S, Liu W, Hou P, Sun W, Yan H. Downregulation of long non-coding RNA nuclear enriched abundant transcript 1 promotes cell proliferation and inhibits cell apoptosis by targeting miR-193a in myocardial ischemia/reperfusion injury. BMC Cardiovasc Disord. 2019;19:192.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Wu HJ, Tang GM, Shao PY, Zou HX, Shen WF, Huang MD, et al. Long non-coding RNA NEAT1 modulates hypoxia/reoxygenation-induced cardiomyocyte injury via targeting microRNA-520a. Exp Ther Med. 2019;18:2199–206.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Luo M, Sun Q, Zhao H, Tao J, Yan D. Long noncoding RNA NEAT1 sponges miR-495-3p to enhance myocardial ischemia-reperfusion injury via MAPK6 activation. J Cell Physiol. 2020;235:105–13.

    Article  PubMed  Google Scholar 

  32. Rui PF, Wang JH, Xu J. Long non-coding NEAT1 weakens the protective role of sevoflurane on myocardial ischemia/reperfusion injury by mediating the microRNA-140/RhoA axis. J Biol Regul Homeost Agents. 2021;35:933–44.

    CAS  PubMed  Google Scholar 

  33. Yao T, Song Y, Li S, Gu J, Yan X. Inhibition of lncRNA NEAT1 protects endothelial cells against hypoxia/reoxygenation‑induced NLRP3 inflammasome activation by targeting the miR‑204/BRCC3 axis. Mol Med Rep. 2022;25:32.

    Article  CAS  PubMed  Google Scholar 

  34. Ramírez CM, Zhang X, Bandyopadhyay C, Rotllan N, Sugiyama MG, Aryal B, et al. Caveolin-1 regulates atherogenesis by attenuating low-density lipoprotein transcytosis and vascular inflammation independently of endothelial nitric oxide synthase activation. Circulation. 2019;140:225–39.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Huang-Fu N, Cheng JS, Wang Y, Li ZW, Wang SH. Neat1 regulates oxidized low-density lipoprotein-induced inflammation and lipid uptake in macrophages via paraspeckle formation. Mol Med Rep. 2018;17:3092-–8.

    PubMed  Google Scholar 

  36. Chen DD, Hui LL, Zhang XC, Chang Q. NEAT1 contributes to ox-LDL-induced inflammation and oxidative stress in macrophages through inhibiting miR-128. J Cell Biochem. 2019;120:2493–501.

    Article  CAS  PubMed  Google Scholar 

  37. Wang L, Xia JW, Ke ZP, Zhang BH. Blockade of NEAT1 represses inflammation response and lipid uptake via modulating miR-342-3p in human macrophages THP-1 cells. J Cell Physiol. 2019;234:5319–26.

    Article  CAS  PubMed  Google Scholar 

  38. Wu X, Chen L, Zeb F, Huang Y, An J, Ren J, et al. Regulation of circadian rhythms by NEAT1 mediated TMAO-induced endothelial proliferation: a protective role of asparagus extract. Exp Cell Res. 2019;382:111451.

    Article  CAS  PubMed  Google Scholar 

  39. Chen L, Wu X, Zeb F, Huang Y, An J, Jiang P, et al. Acrolein-induced apoptosis of smooth muscle cells through NEAT1-Bmal1/Clock pathway and a protection from asparagus extract. Environ Pollut. 2020;258:113735.

    Article  CAS  PubMed  Google Scholar 

  40. Zhang X, Guan MX, Jiang QH, Li S, Zhang HY, Wu ZG, et al. NEAT1 knockdown suppresses endothelial cell proliferation and induces apoptosis by regulating miR‑638/AKT/mTOR signaling in atherosclerosis. Oncol Rep. 2020;44:115–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Guo JT, Wang L, Yu HB. Knockdown of NEAT1 mitigates ox-LDL-induced injury in human umbilical vein endothelial cells via miR-30c-5p/TCF7 axis. Eur Rev Med Pharm Sci. 2020;24:9633–44.

    Google Scholar 

  42. Wang L, Liu J, Lu K, Qiu Y, Li X, Yue F, et al. Long non-coding RNA NEAT1 regulates endothelial functions in subclinical hypothyroidism through miR-126/TRAF7 pathway. Hum Cell. 2021;34:825–35.

    Article  CAS  PubMed  Google Scholar 

  43. Vlachogiannis NI, Sachse M, Georgiopoulos G, Zormpas E, Bampatsias D, Delialis D, et al. Adenosine-to-inosine Alu RNA editing controls the stability of the pro-inflammatory long noncoding RNA NEAT1 in atherosclerotic cardiovascular disease. J Mol Cell Cardiol. 2021;160:111–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Liu A, Zhang Y, Xun S, Sun M. Trimethylamine N-oxide promotes atherosclerosis via regulating the enriched abundant transcript 1/miR-370-3p/signal transducer and activator of transcription 3/flavin-containing monooxygenase-3 axis. Bioengineered. 2022;13:1541–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Fan X, Lou J, Zheng X, Wang Y, Wang J, Luo M, et al. Interference with lncRNA NEAT1 promotes the proliferation, migration, and invasion of trophoblasts by upregulating miR-411-5p and inhibiting PTEN expression. Immunopharmacol Immunotoxicol. 2021;43:334–42.

    Article  CAS  PubMed  Google Scholar 

  46. Zhao L, Xiong M, Liu Y. Baicalin enhances the proliferation and invasion of trophoblasts and suppresses vascular endothelial damage by modulating long non-coding RNA NEAT1/miRNA-205-5p in hypertensive disorder complicating pregnancy. J Obstet Gynaecol Res. 2021;47:3060–70.

    Article  CAS  PubMed  Google Scholar 

  47. Dou X, Ma Y, Qin Y, Dong Q, Zhang S, Tian R, et al. NEAT1 silencing alleviates pulmonary arterial smooth muscle cell migration and proliferation under hypoxia through regulation of miR‑34a‑5p/KLF4 in vitro. Mol Med Rep. 2021;24:749.

    Article  CAS  PubMed  Google Scholar 

  48. Ali MA, Shaker OG, Khalifa AA, Ezzat EM, Elghobary HA, Abdel Mawla TS, et al. LncRNAs NEAT1, HOTAIR, and GAS5 expression in hypertensive and non-hypertensive associated cerebrovascular stroke patients, and its link to clinical characteristics and severity score of the disease. Noncoding RNA Res. 2022;8:96–108.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Zou G, Zhong W, Wu F, Wang X, Liu L. Catalpol attenuates cardiomyocyte apoptosis in diabetic cardiomyopathy via Neat1/miR-140-5p/HDAC4 axis. Biochimie. 2019;165:90–9.

    Article  CAS  PubMed  Google Scholar 

  50. Qin W, Zhao X, Tai J, Qin G, Yu S. Combination of dendrobium mixture and metformin curbs the development and progression of diabetic cardiomyopathy by targeting the lncRNA NEAT1. Clinics (Sao Paulo). 2021;76:e2669.

    Article  PubMed  Google Scholar 

  51. Schiano C, Franzese M, Geraci F, Zanfardino M, Maiello C, Palmieri V, et al. Machine learning and bioinformatics framework integration to potential familial DCM-related markers discovery. Genes (Basel). 2021;12:1946.

    Article  CAS  PubMed  Google Scholar 

  52. Kesherwani V, Shahshahan HR, Mishra PK. Cardiac transcriptome profiling of diabetic Akita mice using microarray and next generation sequencing. PLoS One. 2017;12:e0182828.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Kenneweg F, Bang C, Xiao K, Boulanger CM, Loyer X, Mazlan S, et al. Long noncoding RNA-enriched vesicles secreted by hypoxic cardiomyocytes drive cardiac Fibrosis. Mol Ther Nucleic Acids. 2019;18:363–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Dai H, Zhao N, Liu H, Zheng Y, Zhao L. LncRNA nuclear-enriched abundant transcript 1 regulates atrial fibrosis via the miR-320/NPAS2 axis in atrial fibrillation. Front Pharm. 2021;12:647124.

    Article  CAS  Google Scholar 

  55. Ge Z, Yin C, Li Y, Tian D, Xiang Y, Li Q, et al. Long noncoding RNA NEAT1 promotes cardiac fibrosis in heart failure through increased recruitment of EZH2 to the Smad7 promoter region. J Transl Med. 2022;20:7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Ding JF, Zhou Y, Xu SS, Shi KH, Sun H, Tu B, et al. Epigenetic control of LncRNA NEAT1 enables cardiac fibroblast pyroptosis and cardiac fibrosis. Eur J Pharm. 2023;938:175398.

    Article  CAS  Google Scholar 

  57. Cai B, Yang B, Huang D, Wang D, Tian J, Chen F, et al. STAT3-induced up-regulation of lncRNA NEAT1 as a ceRNA facilitates abdominal aortic aneurysm formation by elevating TULP3. Biosci Rep. 2020;40:BSR20193299.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Shi C, Shen C, Liu G, Yang S, Ye F, Meng J, et al. NEAT1 promotes the repair of abdominal aortic aneurysms of endothelial progenitor cells via regulating miR-204-5p/Ang-1. Am J Transl Res. 2021;13:2111–26.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Gao C, Sun J, Zhang Z, Xu Z. NEAT1 boosts the development of thoracic aortic aneurysm through targeting miR-324-5p/RAN. Arch Med Res. 2022;53:93–9.

    Article  CAS  PubMed  Google Scholar 

  60. Zhou F, Zheng Z, Zha Z, Xiong T, Pan Y. Nuclear paraspeckle assembly transcript 1 enhances hydrogen peroxide-induced human vascular smooth muscle cell injury by regulating miR-30d-5p/A disintegrin and metalloprotease 10. Circ J. 2022;86:1007–18.

    Article  CAS  PubMed  Google Scholar 

  61. Zhuang L, Xia W, Chen D, Ye Y, Hu T, Li S, et al. Exosomal LncRNA-NEAT1 derived from MIF-treated mesenchymal stem cells protected against doxorubicin-induced cardiac senescence through sponging miR-221-3p. J Nanobiotechnol. 2020;18:157.

    Article  CAS  Google Scholar 

Download references

Funding

XJ is supported by National Science Foundation of China (31100834) and National Science Foundation of Shaanxi Province (2020JM-011).

Author information

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, 710061, China

    Xiaoying Jiang

  2. Department of Cardiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004, China

    Mingjuan Zhang

Authors
  1. Xiaoying Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mingjuan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xiaoying Jiang.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

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

Supplementary Information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jiang, X., Zhang, M. The roles of long noncoding RNA NEAT1 in cardiovascular diseases. Hypertens Res 47, 735–746 (2024). https://doi.org/10.1038/s41440-023-01551-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41440-023-01551-0

Keywords

Search

Advanced search

Quick links