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MicroRNA-322-5p targeting Smurf2 regulates the TGF-β/Smad pathway to protect cardiac function and inhibit myocardial infarction

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Abstract

Acute coronary artery blockage leads to acute myocardial infarction (AMI). Cardiomyocytes are terminally differentiated cells that rarely divide. Treatments preventing cardiomyocyte loss during AMI have a high therapeutic benefit. Accumulating evidence shows that microRNAs (miRNAs) may play an essential role in cardiovascular diseases. This study aims to explore the biological function and underlying regulatory molecular mechanism of miR-322-5p on myocardial infarction (MI). This study's miR-322-5p is downregulated in MI-injured hearts according to integrative bioinformatics and experimental analyses. In the MI rat model, miR-322-5p overexpression partially eliminated MI-induced changes in myocardial enzymes and oxidative stress markers, improved MI-caused impairment on cardiac functions, inhibited myocardial apoptosis, attenuated MI-caused alterations in TGF-β, p-Smad2, p-Smad4, and Smad7 protein levels. In oxygen–glucose deprivation (OGD)-injured H9c2 cells, miR-322-5p overexpression partially rescued OGD-inhibited cell viability and attenuated OGD-caused alterations in the TGF-β/Smad signaling. miR-322-5p directly targeted Smurf2 and inhibited Smurf2 expression. In OGD-injured H9c2 cells, Smurf2 knockdown exerted similar effects to miR-322-5p overexpression upon cell viability and TGF-β/Smad signaling; moreover, Smurf2 knockdown partially attenuated miR-322-5p inhibition effects on OGD-injured H9c2 cells. In conclusion, miR-322-5p is downregulated in MI rat heart and OGD-stimulated rat cardiomyocytes; the miR-322-5p/Smurf2 axis improves OGD-inhibited cardiomyocyte cell viability and MI-induced cardiac injuries and dysfunction through the TGF-β/Smad signaling.

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References

  1. Liang H, Su X, Wu Q, et al. LncRNA 2810403D21Rik/Mirf promotes ischemic myocardial injury by regulating autophagy through targeting Mir26a. Autophagy. 2020;16:1077–91.

    Article  CAS  PubMed  Google Scholar 

  2. Qian L, Van Laake LW, Huang Y, Liu S, Wendland MF, Srivastava D. miR-24 inhibits apoptosis and represses Bim in mouse cardiomyocytes. J Exp Med. 2011;208:549–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Orogo AM, Gustafsson AB. Cell death in the myocardium: my heart won’t go on. IUBMB Life. 2013;65:651–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Saadat S, Noureddini M, Mahjoubin-Tehran M, et al. Pivotal role of TGF-beta/Smad signaling in cardiac fibrosis: non-coding RNAs as effectual players. Front Cardiovasc Med. 2020;7:588347.

    Article  CAS  PubMed  Google Scholar 

  5. Dzialo E, Tkacz K, Blyszczuk P. Crosstalk between the TGF-beta and WNT signalling pathways during cardiac fibrogenesis. Acta Biochim Pol. 2018;65:341–9.

    Article  CAS  PubMed  Google Scholar 

  6. Park S, Nguyen NB, Pezhouman A, Ardehali R. Cardiac fibrosis: potential therapeutic targets. Transl Res. 2019;209:121–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Li X, Zhang ZL, Wang HF. Fusaric acid (FA) protects heart failure induced by isoproterenol (ISP) in mice through fibrosis prevention via TGF-beta1/SMADs and PI3K/AKT signaling pathways. Biomed Pharmacother. 2017;93:130–45.

    Article  CAS  PubMed  Google Scholar 

  8. Leask A, Abraham DJ. TGF-beta signaling and the fibrotic response. FASEB J. 2004;18:816–27.

    Article  CAS  PubMed  Google Scholar 

  9. Ikeuchi M, Tsutsui H, Shiomi T, et al. Inhibition of TGF-beta signaling exacerbates early cardiac dysfunction but prevents late remodeling after infarction. Cardiovasc Res. 2004;64:526–35.

    Article  CAS  PubMed  Google Scholar 

  10. Park SH. Fine tuning and cross-talking of TGF-beta signal by inhibitory Smads. J Biochem Mol Biol. 2005;38:9–16.

    PubMed  Google Scholar 

  11. Mattick JS, Makunin V. Non-coding RNA. Hum Mol Genet. 2006;15:17–29.

    Article  Google Scholar 

  12. Xiao Y, Zhao J, Tuazon JP, Borlongan CV, Yu G. MicroRNA-133a and myocardial infarction. Cell Transplant. 2019;28:831–8.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Cruz MS, da Silva AMG, de Souza KSC, Luchessi AD, Silbiger VN. miRNAs emerge as circulating biomarkers of post-myocardial infarction heart failure. Heart Fail Rev. 2020;25:321–9.

    Article  PubMed  Google Scholar 

  14. Wojciechowska A, Braniewska A, Kozar-Kaminska K. MicroRNA in cardiovascular biology and disease. Adv Clin Exp Med. 2017;26:865–74.

    Article  PubMed  Google Scholar 

  15. Wang GK, Zhu JQ, Zhang JT, et al. Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. Eur Heart J. 2010;31:659–66.

    Article  PubMed  Google Scholar 

  16. Ai J, Zhang R, Li Y, et al. Circulating microRNA-1 as a potential novel biomarker for acute myocardial infarction. Biochem Biophys Res Commun. 2010;391:73–7.

    Article  CAS  PubMed  Google Scholar 

  17. Yang B, Lin H, Xiao J, et al. The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2. Nat Med. 2007;13:486–91.

    Article  CAS  PubMed  Google Scholar 

  18. Luo X, Pan Z, Shan H, et al. MicroRNA-26 governs profibrillatory inward-rectifier potassium current changes in atrial fibrillation. J Clin Invest. 2013;123:1939–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Liu Y, Wang Z, Xiao W. MicroRNA-26a protects against cardiac hypertrophy via inhibiting GATA4 in rat model and cultured cardiomyocytes. Mol Med Rep. 2016;14:2860–6.

    Article  CAS  PubMed  Google Scholar 

  20. Zhang Y, Qin W, Zhang L, et al. MicroRNA-26a prevents endothelial cell apoptosis by directly targeting TRPC6 in the setting of atherosclerosis. Sci Rep. 2015;5:9401.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ren XP, Wu J, Wang X, et al. MicroRNA-320 is involved in the regulation of cardiac ischemia/reperfusion injury by targeting heat-shock protein 20. Circulation. 2009;119:2357–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. van Rooij E, Sutherland LB, Thatcher JE, et al. Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. Proc Natl Acad Sci U S A. 2008;105:13027–32.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Rane S, He M, Sayed D, et al. Downregulation of miR-199a derepresses hypoxia-inducible factor-1alpha and Sirtuin 1 and recapitulates hypoxia preconditioning in cardiac myocytes. Circ Res. 2009;104:879–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Atri C, Guerfali FZ, Laouini D (2019) MicroRNAs in diagnosis and therapeutics. In Editor B Mallick, Ago driven Non coding RNAs, Academic Press, Amsterdam

  25. Martinez B, Peplow PV. MicroRNAs in mouse and rat models of experimental epilepsy and potential therapeutic targets. Neural Regen Res. 2023;18:2108–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wu A, Lou L, Zhai J, et al. miRNA Expression Profile and Effect of Wenxin Granule in Rats with Ligation-Induced Myocardial Infarction. Int J Genomics. 2017;2017:2175871.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Rizzo SA, Bartley O, Rosser AE, Newland B. Oxygen-glucose deprivation in neurons: implications for cell transplantation therapies. Prog Neurobiol. 2021;205:102126.

    Article  CAS  PubMed  Google Scholar 

  28. Zhang X, Chen Q, Zhao J, et al. A four-compound remedy AGILe protected H9c2 cardiomyocytes against oxygen glucose deprivation via targeting the TNF-α/NF-κB pathway: Implications for the therapy of myocardial infarction. Front Pharmacol. 2023;14:1050970.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Di Leva G, Garofalo M, Croce CM. MicroRNAs in cancer. Annu Rev Pathol. 2014;9:287–314.

    Article  PubMed  Google Scholar 

  30. Fabian MR, Sonenberg N, Filipowicz W. Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem. 2010;79:351–79.

    Article  CAS  PubMed  Google Scholar 

  31. Ghosh G, Subramanian IV, Adhikari N, et al. Hypoxia-induced microRNA-424 expression in human endothelial cells regulates HIF-alpha isoforms and promotes angiogenesis. J Clin Invest. 2010;120:4141–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Youn SW, Li Y, Kim YM, et al. Modification of cardiac progenitor cell-derived exosomes by miR-322 provides protection against myocardial infarction through nox2-dependent angiogenesis. Antioxidants. 2019;8:18.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Long Y, Wang L, Li Z. SP1-induced SNHG14 aggravates hypertrophic response in in vitro model of cardiac hypertrophy via up-regulation of PCDH17. J Cell Mol Med. 2020;24:7115–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Ruan Y, Meng S, Jia R, Cao X. MicroRNA-322-5p protects against myocardial infarction through targeting BTG2. Am J Med Sci. 2021. https://doi.org/10.1016/j.amjms.2024.02.012.

    Article  Google Scholar 

  35. Zeng Y, Liu H, Kang K, et al. Hypoxia inducible factor-1 mediates expression of miR-322: potential role in proliferation and migration of pulmonary arterial smooth muscle cells. Sci Rep. 2015;5:12098.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Merlet E, Atassi F, Motiani RK, et al. miR-424/322 regulates vascular smooth muscle cell phenotype and neointimal formation in the rat. Cardiovasc Res. 2013;98:458–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Shen X, Soibam B, Benham A, et al. miR-322/-503 cluster is expressed in the earliest cardiac progenitor cells and drives cardiomyocyte specification. Proc Natl Acad Sci U S A. 2016;113:9551–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Cai X, Wang S, Hong L, et al. Inhibition of miR-322-5p protects cardiac myoblast cells against hypoxia-induced apoptosis and injury through regulating CIAPIN1. J Cardiovasc Pharmacol. 2021;77:200–7.

    Article  CAS  PubMed  Google Scholar 

  39. Li D, Wang X, Huang Q, Li S, Zhou Y, Li Z. Cardioprotection of CAPE-oNO2 against myocardial ischemia/reperfusion induced ROS generation via regulating the SIRT1/eNOS/NF-kappaB pathway in vivo and in vitro. Redox Biol. 2018;15:62–73.

    Article  CAS  PubMed  Google Scholar 

  40. Ottani A, Neri L, Canalini F, et al. Protective effects of the melanocortin analog NDP-alpha-MSH in rats undergoing cardiac arrest. Eur J Pharmacol. 2014;745:108–16.

    Article  CAS  PubMed  Google Scholar 

  41. Emadi N, Nemati MH, Ghorbani M, Allahyari E. The effect of high-dose vitamin C on biochemical markers of myocardial injury in coronary artery bypass surgery. Braz J Cardiovasc Surg. 2019;34:517–24.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Zhang Q, Ju Y, Ma Y, Wang T. N-acetylcysteine improves oxidative stress and inflammatory response in patients with community acquired pneumonia: a randomized controlled trial. Medicine. 2018;97:e13087.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Santos CX, Anilkumar N, Zhang M, Brewer AC, Shah AM. Redox signaling in cardiac myocytes. Free Radic Biol Med. 2011;50:777–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Teringova E, Tousek P. Apoptosis in ischemic heart disease. J Transl Med. 2017;15:87.

    Article  PubMed  PubMed Central  Google Scholar 

  45. David D, Nair SA, Pillai MR. Smurf E3 ubiquitin ligases at the cross roads of oncogenesis and tumor suppression. Biochim Biophys Acta. 2013;1835:119–28.

    CAS  PubMed  Google Scholar 

  46. Han Li C, Chen Y. Targeting EZH2 for cancer therapy: progress and perspective. Curr Protein Pept Sci. 2015;16:559–70.

    Article  PubMed  Google Scholar 

  47. Tan JZ, Yan Y, Wang XX, Jiang Y, Xu HE. EZH2: biology, disease, and structure-based drug discovery. Acta Pharmacol Sin. 2014;35:161–74.

    Article  CAS  PubMed  Google Scholar 

  48. Cao S, Xiao L, Rao JN, et al. Inhibition of Smurf2 translation by miR-322/503 modulates TGF-beta/Smad2 signaling and intestinal epithelial homeostasis. Mol Biol Cell. 2014;25:1234–43.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Dong W, Xie F, Chen XY, et al. Inhibition of Smurf2 translation by miR-322/503 protects from ischemia-reperfusion injury by modulating EZH2/Akt/GSK3beta signaling. Am J Physiol Cell Physiol. 2019;317:C253–61.

    Article  CAS  PubMed  Google Scholar 

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Funding

This study was supported by the Scientific Research Incentive Fund of Shanxi Cardiovascular Hospital (no. XYS20180206) and the Shanxi Provincial Health Commission “Four Batch Science and Technology Innovation Project of Medical Development" (no. 2021XM45).

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Authors and Affiliations

  1. Department of Cardiology, Shanxi Cardiovascular Hospital, Taiyuan, 030000, Shanxi, China

    Liping Guo, Huaiming Niu, Jun Li, Xin Shao, Na Li, Yuehui Sun & Haixiong Wang

  2. Department of Cardiology, The People’s Hospital of Suzhou, Suzhou New District, Suzhou, 215129, Jiangsu, China

    Ke Li

  3. Department of General Practice, Taiyuan Central Hospital, Taiyuan, 030000, Shanxi, China

    Yan Ma

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  1. Liping Guo
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Correspondence to Haixiong Wang.

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All the animal experimental procedures were approved by the Ethics Committee of Shanxi Cardiovascular Hospital (approval number: NO20200509).

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Guo, L., Li, K., Ma, Y. et al. MicroRNA-322-5p targeting Smurf2 regulates the TGF-β/Smad pathway to protect cardiac function and inhibit myocardial infarction. Human Cell 37, 972–985 (2024). https://doi.org/10.1007/s13577-024-01062-1

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