Abstract

Background. Viral myocarditis (VMC) is common in children. Previous studies have reported the clinical value of nuclear paraspeckle assembly transcript 1 (NEAT1) and microRNA-425-3p (miR-425-3p) in certain diseases, but not in VMC. This article was designed to investigate the expression of long noncoding RNA (lncRNA) NEAT1 and miR-425-3p in the serum of patients with VMC and their clinical significance.

Methods. We assessed VMC and healthy patients and analyzed differences in the expression levels of NEAT1 and miR-425-3p. The correlation and targeting relationship between the two were reported by Spearman correlation analysis and luciferase reporter assay. ROC curves were plotted to reflect the diagnostic effect of both. In addition, according to the 12-month prognostic effect grouping, patients with VMC were separated into a group with good vs. poor prognosis, and the difference in the expression levels of NEAT1 and miR-425-3p between the two groups were analyzed. The ability of the two markers in the prognosis of VMC was further analyzed by multiple logistic regression.

Results. NEAT1 expression was up-regulated in VMC and miR-425-3p expression was down-regulated, and there was a negative correlation and targeting link between the two. The diagnostic efficacy of both NEAT1 and miR-425-3p was higher than that of a single indicator. High expression of NEAT1 and low expression of miR-425-3p were found in VMC patients with poor prognosis. Both were independent influencers of VMC prognosis.

Conclusion. NEAT1 and miR-425-3p expressions were affected by VMC and had important clinical implications for VMC, indicating for the first time the clinical function of NEAT1 and miR-425-3p in VMC.

Keywords: NEAT1, miR-425-3p, viral myocarditis, diagnosis, prognosis

Copyright and license

How to cite

1.
Gao J, Qin L, Guo Q, et al. Diagnostic value and clinical significance of lncRNA NEAT1 combined with miR-425-3p in children with viral myocarditis. Turk J Pediatr 2024; 66: 439-447. https://doi.org/10.24953/turkjpediatr.2024.4579

References

  1. Zhou J, Xu J, Li P, et al. Necroptosis and viral myocarditis: tumor necrosis factor α as a novel biomarker for the diagnosis of viral myocarditis. Front Cell Dev Biol 2022; 10: 826904. https://doi.org/10.3389/fcell.2022.826904
  2. Deckx S, Johnson DM, Rienks M, et al. Extracellular SPARC increases cardiomyocyte contraction during health and disease. PLoS One 2019; 14: e0209534. https://doi.org/10.1371/journal.pone.0209534
  3. Yue-Chun L, Gu XH, Li-Sha G, et al. Vagus nerve plays a pivotal role in CD4+ T cell differentiation during CVB3-induced murine acute myocarditis. Virulence 2021; 12: 360-376. https://doi.org/10.1080/21505594.2020.1869384
  4. Narovlyanskaya O, Winokur EJ. Viral myocarditis. Dimens Crit Care Nurs 2020; 39: 75-80. https://doi.org/10.1097/DCC.0000000000000402
  5. Yan M, Wang J, Wang S, Zhang Y, Liu L, Zhao H. Expression levels of microRNA-146b and anti-cardiac troponin I in serum of children with viral myocarditis and their clinical significance. Iran J Public Health 2021; 50: 510-519. https://doi.org/10.18502/ijph.v50i3.5592
  6. Liu H, Li M, Song Y, Xu W. TRIM21 restricts coxsackievirus B3 replication, cardiac and pancreatic injury via interacting with MAVS and positively regulating IRF3-mediated type-I interferon production. Front Immunol 2018; 9: 2479. https://doi.org/10.3389/fimmu.2018.02479
  7. Zhang C, Xiong Y, Zeng L, et al. The role of non-coding RNAs in viral myocarditis. Front Cell Infect Microbiol 2020; 10: 312. https://doi.org/10.3389/fcimb.2020.00312
  8. He F, Liu Z, Feng M, et al. The lncRNA MEG3/miRNA-21/P38MAPK axis inhibits coxsackievirus 3 replication in acute viral myocarditis. Virus Res 2024; 339: 199250. https://doi.org/10.1016/j.virusres.2023.199250
  9. Xue Y, Ke J, Zhou X, et al. Knockdown of LncRNA MALAT1 alleviates coxsackievirus B3-induced acute viral myocarditis in mice via inhibiting Th17 cells differentiation. Inflammation 2022; 45: 1186-1198. https://doi.org/10.1007/s10753-021-01612-x
  10. Zhang N, Sun Y. LncRNA ROR facilitates myocardial fibrosis in rats with viral myocarditis through regulating C-Myc expression. Eur Rev Med Pharmacol Sci 2019; 23: 10982-10988. https://doi.org/10.26355/eurrev_201912_19803
  11. Wang SM, Liu GQ, Xian HB, Si JL, Qi SX, Yu YP. LncRNA NEAT1 alleviates sepsis-induced myocardial injury by regulating the TLR2/NF-κB signaling pathway. Eur Rev Med Pharmacol Sci 2019; 23: 4898-4907. https://doi.org/10.26355/eurrev_201906_18078
  12. 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. https://doi.org/10.1016/j.gene.2019.144324
  13. Marketou M, Kontaraki J, Patrianakos A, et al. Peripheral blood microRNAs as potential biomarkers of myocardial damage in acute viral myocarditis. Genes (Basel) 2021; 12: 420. https://doi.org/10.3390/genes12030420
  14. Li J, Tu J, Gao H, Tang L. MicroRNA-425-3p inhibits myocardial inflammation and cardiomyocyte apoptosis in mice with viral myocarditis through targeting TGF-β1. Immun Inflamm Dis 2021; 9: 288-298. https://doi.org/10.1002/iid3.392
  15. Wu T, Diagnostic criteria for viral myocarditis (draft revision). Chinese Journal of Practical Pediatrics. 2000;15.
  16. Olejniczak M, Schwartz M, Webber E, Shaffer A, Perry TE. Viral myocarditis-incidence, diagnosis and management. J Cardiothorac Vasc Anesth 2020; 34: 1591-1601. https://doi.org/10.1053/j.jvca.2019.12.052
  17. Putschoegl A, Auerbach S. Diagnosis, evaluation, and treatment of myocarditis in children. Pediatr Clin North Am 2020; 67: 855-874. https://doi.org/10.1016/j.pcl.2020.06.013
  18. Adeboye A, Alkhatib D, Butt A, Yedlapati N, Garg N. A review of the role of imaging modalities in the evaluation of viral myocarditis with a special focus on COVID-19-related myocarditis. Diagnostics (Basel) 2022; 12: 549. https://doi.org/10.3390/diagnostics12020549
  19. Xue Y, Ke J, Zhang J, et al. Analysis of long noncoding RNAs and messenger RNAs expression profiles in the hearts of mice with acute viral myocarditis. J Med Virol 2023; 95: e28473. https://doi.org/10.1002/jmv.28473
  20. Cao H, Yang B, Zhao Y, Deng X, Shen X. The pro-apoptosis and pro-inflammation role of LncRNA HIF1A-AS1 in Coxsackievirus B3-induced myocarditis via targeting miR-138. Cardiovasc Diagn Ther 2020; 10: 1245-1255. https://doi.org/10.21037/cdt-20-545
  21. Xue Y, Zhang J, Ke J, et al. LncGBP9 knockdown alleviates myocardial inflammation and apoptosis in mice with acute viral myocarditis via suppressing NF-κB signaling pathway. Inflamm Res 2022; 71: 1559-1576. https://doi.org/10.1007/s00011-022-01644-5
  22. Zhang Y, Li X, Kong X, et al. Long non-coding RNA AK085865 ablation confers susceptibility to viral myocarditis by regulating macrophage polarization. J Cell Mol Med 2020; 24: 5542-5554. https://doi.org/10.1111/jcmm.15210
  23. 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: 15307-15319. https://doi.org/10.18632/aging.203089
  24. Ge Z, Yin C, Li Y, 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. https://doi.org/10.1186/s12967-021-03211-8
  25. Ferragut Cardoso AP, Banerjee M, Nail AN, Lykoudi A, States JC. miRNA dysregulation is an emerging modulator of genomic instability. Semin Cancer Biol 2021; 76: 120-131. https://doi.org/10.1016/j.semcancer.2021.05.004
  26. Zhang Y, Sun L, Sun H, et al. MicroRNA-381 protects myocardial cell function in children and mice with viral myocarditis via targeting cyclooxygenase-2 expression. Exp Ther Med 2018; 15: 5510-5516. https://doi.org/10.3892/etm.2018.6082
  27. Zhang Z, Dai X, Qi J, Ao Y, Yang C, Li Y. Astragalus mongholicus (Fisch.) Bge improves peripheral treg cell immunity imbalance in the children with viral myocarditis by reducing the levels of miR-146b and miR-155. Front Pediatr 2018; 6: 139. https://doi.org/10.3389/fped.2018.00139
  28. Wang L, Liu J, Xu B, Liu YL, Liu Z. Reduced exosome miR-425 and miR-744 in the plasma represents the progression of fibrosis and heart failure. Kaohsiung J Med Sci 2018; 34: 626-633. https://doi.org/10.1016/j.kjms.2018.05.008