Download PDF
Thorac Cardiovasc Surg
DOI: 10.1055/s-0044-1786528
Original Basic Science

miR-92b-3p Protects against Myocardial Ischemia-Reperfusion Injury by Inhibiting MAP3K2 in a Mouse Model

Kun Zhao
1   Department of Emergency, Second Hospital of Hebei Medical University, East Campus, Shijiazhuang, Hebei, China
,
Mei Wang
2   Department of Cardiovascular Medicine, Second Hospital of Hebei Medical University, East Branch, Shijiazhuang, Hebei, China
› Author Affiliations Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
› Further Information
    Permissions and Reprints All articles of this category

Abstract

Objective MicroRNAs are well-known RNA regulators modulating biological functions in complex signaling networks. This work aims to explore the impact of microRNA-92b-3p (miR-92b-3p) on myocardial ischemia-reperfusion (I/R) injury.

Materials and Methods The I/R model was established by left anterior descending coronary artery ligation in mice. The hemodynamic parameters were detected through a multichannel physiological recorder. Myocardial injury markers: serum cardiac troponin I, myocardial kinase isoenzyme (creatine kinase-MB), and serum inflammatory factors (tumor necrosis factor-α, interleukin [IL]-1β, and IL-6) were evaluated by enzyme-linked immunosorbent assay. Cardiac tissue oxidative stress-related factors (malondialdehyde, glutathione peroxidase, total antioxidation capability, and superoxide dismutase) were assessed by colorimetry, myocardial pathology was observed by hematoxylin–eosin staining, and cardiomyocyte apoptosis was measured by triphosphate nick end-labeling staining, as well as the expression of miR-92b-3p and mitogen-activated protein kinase kinase kinase 2 (MAP3K2) in cardiac tissues were determined by reverse transcription quantitative polymerase chain reaction or western blot assay. The targeting relationship between miR-92b-3p and MAP3K2 was verified by bioinformatics, RNA immunoprecipitation, and luciferase reporter assays.

Results miR-92b-3p was lowly expressed and MAP3K2 was highly expressed in myocardial I/R injury mice. Upregulation of miR-92b-3p improved hemodynamic indices, decreased serum levels of myocardial injury biomarkers, inhibited serum inflammatory response, alleviated cardiac tissue oxidative stress, relieved myocardial pathology, and reduced cardiomyocyte apoptosis during the myocardial I/R injury in mice. MAP3K2 was a direct target gene of miR-92b-3p.

Conclusion This research suggests that miR-92b-3p protects against myocardial I/R injury by inhibiting MAP3K2, which may provide novel candidates for treatment of myocardial I/R injury.

Keywords

microRNA-92b-3p - mitogen-activated protein kinase kinase kinase 2 - myocardial ischemia-reperfusion injury - myocardial infarction - apoptosis

Supplementary Material



Publication History

Received: 03 August 2023

Accepted: 25 March 2024

Article published online:
01 May 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Sugiyama A, Mitsui A, Okada M, Yamawaki H. Cathepsin S degrades arresten and canstatin in infarcted area after myocardial infarction in rats. J Vet Med Sci 2019; 81 (04) 522-531
    CrossrefPubMedGoogle Scholar
  • 2 Chen G, Yang L, Zhong L. et al. Delivery of hydrogen sulfide by ultrasound targeted microbubble destruction attenuates myocardial ischemia-reperfusion injury. Sci Rep 2016; 6: 30643
    CrossrefPubMedGoogle Scholar
  • 3 Wang N, Song G, Yang Y, Yuan W, Qi M. Inactivated Lactobacillus promotes protection against myocardial ischemia-reperfusion injury through NF-κB pathway. Biosci Rep 2017; 37 (06) BSR20171025
    CrossrefPubMedGoogle Scholar
  • 4 Lee FY, Shao PL, Wallace CG. et al. Combined therapy with SS31 and mitochondria mitigates myocardial ischemia-reperfusion injury in rats. Int J Mol Sci 2018; 19 (09) 2782
    CrossrefPubMedGoogle Scholar
  • 5 Marinescu MC, Lazar AL, Marta MM, Cozma A, Catana CS. Non-coding RNAs: prevention, diagnosis, and treatment in myocardial ischemia-reperfusion injury. Int J Mol Sci 2022; 23 (05) 2728
    CrossrefPubMedGoogle Scholar
  • 6 Liu L, Wang D, Qiu Y, Dong H, Zhan X. Overexpression of microRNA-15 increases the chemosensitivity of colon cancer cells to 5-fluorouracil and oxaliplatin by inhibiting the nuclear factor-κB signalling pathway and inducing apoptosis. Exp Ther Med 2018; 15 (03) 2655-2660
    PubMedGoogle Scholar
  • 7 Kunecki M, Płazak W, Podolec P, Gołba KS. Effects of endogenous cardioprotective mechanisms on ischemia-reperfusion injury. Postepy Hig Med Dosw 2017; 71 (00) 20-31
    CrossrefPubMedGoogle Scholar
  • 8 Li Y, Li Z, Liu J, Liu Y, Miao G. miR-190-5p alleviates myocardial ischemia-reperfusion injury by targeting PHLPP1. Dis Markers 2021; 2021: 8709298
    PubMedGoogle Scholar
  • 9 Zhou M, Cai J, Tang Y, Zhao Q. MiR-17-92 cluster is a novel regulatory gene of cardiac ischemic/reperfusion injury. Med Hypotheses 2013; 81 (01) 108-110
    CrossrefPubMedGoogle Scholar
  • 10 Xu L, Cao H, Xie Y. et al. Exosome-shuttled miR-92b-3p from ischemic preconditioned astrocytes protects neurons against oxygen and glucose deprivation. Brain Res 2019; 1717: 66-73
    CrossrefPubMedGoogle Scholar
  • 11 Yu XJ, Huang YQ, Shan ZX. et al. MicroRNA-92b-3p suppresses angiotensin II-induced cardiomyocyte hypertrophy via targeting HAND2. Life Sci 2019; 232: 116635
    CrossrefPubMedGoogle Scholar
  • 12 Lee J, Heo J, Kang H. miR-92b-3p-TSC1 axis is critical for mTOR signaling-mediated vascular smooth muscle cell proliferation induced by hypoxia. Cell Death Differ 2019; 26 (09) 1782-1795
    CrossrefPubMedGoogle Scholar
  • 13 Ben-Zvi I, Volinsky N, Grosman-Rimon L. et al. Cardiac-peripheral transvenous gradients of microRNA expression in systolic heart failure patients. ESC Heart Fail 2020; 7 (03) 835-843
    CrossrefPubMedGoogle Scholar
  • 14 Fu DL, Jiang H, Li CY, Gao T, Liu MR, Li HW. MicroRNA-338 in MSCs-derived exosomes inhibits cardiomyocyte apoptosis in myocardial infarction. Eur Rev Med Pharmacol Sci 2020; 24 (19) 10107-10117
    PubMedGoogle Scholar
  • 15 Wang AD, Dai LF, Yang L. et al. Upregulation of miR-335 reduces myocardial injury following myocardial infarction via targeting MAP3K2. Eur Rev Med Pharmacol Sci 2021; 25 (01) 344-352
    PubMedGoogle Scholar
  • 16 Hausenloy DJ, Yellon DM. Myocardial ischemia-reperfusion injury: a neglected therapeutic target. J Clin Invest 2013; 123 (01) 92-100
    CrossrefPubMedGoogle Scholar
  • 17 Liu B, Wu X, Liu B. et al. MiR-26a enhances metastasis potential of lung cancer cells via AKT pathway by targeting PTEN. Biochim Biophys Acta 2012; 1822 (11) 1692-1704
    CrossrefPubMedGoogle Scholar
  • 18 Peterlin A, Počivavšek K, Petrovič D, Peterlin B. The role of microRNAs in heart failure: a systematic review. Front Cardiovasc Med 2020; 7: 161
    CrossrefPubMedGoogle Scholar
  • 19 Ji R, Cheng Y, Yue J. et al. MicroRNA expression signature and antisense-mediated depletion reveal an essential role of MicroRNA in vascular neointimal lesion formation. Circ Res 2007; 100 (11) 1579-1588
    CrossrefPubMedGoogle Scholar
  • 20 Goren Y, Kushnir M, Zafrir B, Tabak S, Lewis BS, Amir O. Serum levels of microRNAs in patients with heart failure. Eur J Heart Fail 2012; 14 (02) 147-154
    CrossrefPubMedGoogle Scholar
  • 21 Taurino C, Miller WH, McBride MW. et al. Gene expression profiling in whole blood of patients with coronary artery disease. Clin Sci (Lond) 2010; 119 (08) 335-343
    CrossrefPubMedGoogle Scholar
  • 22 Borosch S, Dahmen E, Beckers C. et al. Characterization of extracellular vesicles derived from cardiac cells in an in vitro model of preconditioning. J Extracell Vesicles 2017; 6 (01) 1390391
    CrossrefPubMedGoogle Scholar
  • 23 Chen Z, Li Z, Jiang C, Jiang X, Zhang J. MiR-92b-3p promotes neurite growth and functional recovery via the PTEN/AKT pathway in acute spinal cord injury. J Cell Physiol 2019; 234 (12) 23043-23052
    CrossrefPubMedGoogle Scholar
  • 24 Yuan Q, Basit A, Liang W. et al. Pazopanib ameliorates acute lung injuries via inhibition of MAP3K2 and MAP3K3. Sci Transl Med 2021; 13 (591) eabc2499
    CrossrefPubMedGoogle Scholar
  • 25 Fabian MR, Sonenberg N. The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC. Nat Struct Mol Biol 2012; 19 (06) 586-593
    CrossrefPubMedGoogle Scholar
  • 26 Xu W, Qian L, Yuan X, Lu Y. Regulation of a novel CircTRRAP/miR-761/MAP3K2 CeRNA cascade in inflammation, apoptosis, and oxidative stress in human AC16 cardiomyocytes under hypoxia conditions. Int Heart J 2023; 64 (03) 442-452
    CrossrefPubMedGoogle Scholar
  • 27 Liu E, Sun H, Wu J, Kuang Y. MiR-92b-3p regulates oxygen and glucose deprivation-reperfusion-mediated apoptosis and inflammation by targeting TRAF3 in PC12 cells. Exp Physiol 2020; 105 (10) 1792-1801
    CrossrefPubMedGoogle Scholar