Article Data

  • Views 1769
  • Dowloads 173

Original Research

Open Access

miR-187 modulates cardiomyocyte apoptosis and oxidative stress in myocardial infarction mice via negatively regulating DYRK2

  • Fen Zhu1
  • Zhili Yu1
  • Dongsheng Li1

1Department of Cardiology, Wuhan Third Hospital & Tongren Hospital of Wuhan University, 430060 Wuhan, Hubei, China

DOI: 10.22514/sv.2021.137 Vol.17,Issue 5,September 2021 pp.142-150

Submitted: 13 May 2021 Accepted: 30 July 2021

Published: 08 September 2021

*Corresponding Author(s): Fen Zhu E-mail:


Myocardial infarction is a serious representation of cardiovescular disease, MicroRNAs play a role in modifying I/R injury and myocardial infarct remodeling. The present study therefore examined the potential role of miR-187 in cardiac I/R injury and its underlying mechanisms. miR-187 was inhibited or overexpressed in cardiomyocytes H/R models by pretreatment with miR-187 mimic or inhibitor to confirm the function of miR-187 in H/R. DYRK2 was inhibited or overexpressed in cardiomyocytes H/R models by pretreatment with DYRK2 inhibitor. A myocardium I/R mouse model was established. Circulating levels of miR-187 or DYRK2 was detected by quantitative realtime PCR and protein expression was detected by western blotting. The cell viability in all groups was determined by MTT assay and the apoptosis ratio was detected by flow cytometry after staining with Annexin V-FITC. The effect of miR-187 on cellular ROS generation was examined by DCFH-DA. The level of lipid peroxidation and SOD expression were determined by MDA and SOD assay. The findings indicated that miR-187 may be a possible regulator in the protective effect of H/R-induced cardiomyocyte apoptosis, cellular oxidative stress and leaded to DYRK2 suppression at a posttranscriptional level. Moreover, the improvement of miR-187 on H/R-induced cardiomyocyte injury contributed to the obstruction of DYRK2 expression. In addition, these results identified DYRK2 as the functional downstream target of miR-187 regulated myocardial infarction and oxidative stress.These present work provided the first insight into the function of miR-187 in successfully protect cardiomyocyte both in vivo and in vitro, and such a protective effect were mediated through the regulation of DYRK2 expression.


miR-187; DYRK2; Cardiomyocyte; Myocardial infarction; Oxidative stress

Cite and Share

Fen Zhu,Zhili Yu,Dongsheng Li. miR-187 modulates cardiomyocyte apoptosis and oxidative stress in myocardial infarction mice via negatively regulating DYRK2. Signa Vitae. 2021. 17(5);142-150.


[1] Wang ZH, Pan JH, Ma XP, Xu XY, Yu WH, Fu WJ et al. Cardioprotective effect of Shenxiong glucose injection on acute myocardial infarction in rats via reduction in myocardial intracellular calcium ion overload. Tropical Journal of Pharmaceutical Research. 2017; 16: 1097–1104.

[2] Sedding DG, Boyle EC, Demandt JAF, Sluimer JC, Dutzmann J, Haverich A, et al. Vasa vasorum angiogenesis: key player in the initiation and progression of atherosclerosis and potential target for the treatment of cardiovascular disease. Frontiers in Immunology. 2018; 9: 706.

[3] Maznyczka A, Kaier T, Marber M. Troponins and other biomarkers in the early diagnosis of acute myocardial infarction. Postgraduate Medical Journal. 2015; 91: 322–330.

[4] Zimetbaum PJ, Josephson ME. Use of the electrocardiogram in acute myocardial infarction. New England Journal of Medicine. 2003; 348: 933–940.

[5] Steg PG, James SK, Atar D, Badano LP, Blömstrom-Lundqvist C, Borger MA, et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC). European Heart Journal. 2012; 33: 2569–2619.

[6] Nishikawa H, Taniguchi Y, Matsumoto T, Arima N, Masaki M, Shima-mura Y, et al. Knockout of the interleukin-36 receptor protects against renal ischemia-reperfusion injury by reduction of proinflammatory cytokines. Kidney International. 2018; 93: 599–614.

[7] Bagheri F, Khori V, Alizadeh AM, Khalighfard S, Khodayari S, Khodayari H. Reactive oxygen species-mediated cardiac-reperfusion injury: Mechanisms and therapies. Life Sciences. 2016; 165: 43–55.

[8] Chang JC, Lien CF, Lee WS, Chang HR, Hsu YC, Luo YP, et al. Intermittent hypoxia prevents myocardial mitochondrial Ca2+ overload and cell death during ischemia/reperfusion: the role of reactive oxygen species. Cells. 2019; 8: 564.

[9] Xue J, Yan X, Yang Y, Chen M, Wu L, Gou Z, et al. Connexin 43 dephosphorylation contributes to arrhythmias and cardiomyocyte apoptosis in ischemia/reperfusion hearts. Basic Research in Cardiology. 2019; 114: 40.

[10] Diniz GP, Lino CA, Moreno CR, Senger N, Barreto-Chaves MLM. MicroRNA-1 overexpression blunts cardiomyocyte hypertrophy elicited by thyroid hormone. Journal of Cellular Physiology. 2017; 232: 3360–3368.

[11] Chen Z, Wang H, Xia Y, Yan F, Lu Y. Therapeutic Potential of Mesenchymal Cell-Derived miRNA-150-5p-Expressing Exosomes in Rheumatoid Arthritis Mediated by the Modulation of MMP14 and VEGF. Journal of Immunology. 2018; 201: 2472–2482.

[12] Zhai C, Qian Q, Tang G, Han B, Hu H, Yin D, et al. MicroRNA-206 Protects against Myocardial Ischaemia-Reperfusion Injury in Rats by Targeting Gadd45β. Molecules and Cells. 2017; 40: 916–924.

[13] Zhao C, Zhou B, Cao J, Zhang Y, Li W, Wang M, et al. miR-187-3p participates in contextual fear memory formation through modulating SATB2 expression in the hippocampus. NeuroReport. 2020; 31: 909–917.

[14] Fay MJ, Alt LAC, Ryba D, Salamah R, Peach R, Papaeliou A, et al. Cadmium Nephrotoxicity is Associated with Altered MicroRNA Expression in the Rat Renal Cortex. Toxics. 2018; 6: 16.

[15] Yan H, Hu K, Wu W, Li Y, Tian H, Chu Z, et al. Low Expression of DYRK2 (Dual Specificity Tyrosine Phosphorylation Regulated Kinase 2) Correlates with Poor Prognosis in Colorectal Cancer. PLoS ONE. 2016; 11: e0159954.

[16] Yoshida S, Yoshida K. Multiple functions of DYRK2 in cancer and tissue development. FEBS Letters. 2019; 593: 2953–2965.

[17] National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals. Guide for the Care and Use of Laboratory Animals. 8th edition. Washington (DC): National Academies Press. 2011.

[18] Schumer M, Colombel MC, Sawczuk IS, Gobé G, Connor J, O’Toole KM, et al. Morphologic, biochemical, and molecular evidence of apoptosis during the reperfusion phase after brief periods of renal ischemia. American Journal of Pathology. 1992; 140: 831–838.

[19] Huang G, Hao F, Hu X. Downregulation of microRNA‐155 stim-ulates sevoflurane‐mediated cardioprotection against myocardial is-chemia/reperfusion injury by binding to SIRT1 in mice. Journal of Cellular Biochemistry. 2019; 120: 15494–15505.

[20] MacPhee DJ. Methodological considerations for improving Western blot analysis. Journal of Pharmacological and Toxicological Methods. 2010; 61: 171–177.

[21] Aranda A, Sequedo L, Tolosa L, Quintas G, Burello E, Castell JV, et al. Dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay: a quantitative method for oxidative stress assessment of nanoparticle-treated cells. Toxicology in Vitro. 2013; 27: 954–963.

[22] Alamer A, Ali D, Alarifi S, Alkahtane A, AL-Zharani M, Abdel-Daim MM, et al. Bismuth oxide nanoparticles induce oxidative stress and apoptosis in human breast cancer cells. Environmental Science and Pollution Research. 2021; 28: 7379–7389.

[23] Van Linthout S, Tschöpe C. Inflammation—Cause or Consequence of Heart Failure or both? Current Heart Failure Reports. 2017; 14: 251–265.

[24] Sun T, Li M, Li P, Cao J. MicroRNAs in Cardiac Autophagy: Small Molecules and Big Role. Cells. 2018; 7: 104.

[25] Sun C, Li S, Yang C, Xi Y, Wang L, Zhang F, et al. MicroRNA-187-3p mitigates non-small cell lung cancer (NSCLC) development through down-regulation of BCL6. Biochemical and Biophysical Research Communications. 2016; 471: 82–88.

[26] Weber M, Baker MB, Patel RS, Quyyumi AA, Bao G, Searles CD. MicroRNA Expression Profile in CAD Patients and the Impact of ACEI/ARB. Cardiology Research and Practice. 2011; 2011: 532915.

[27] Nihira NT, Yoshida K. Engagement of DYRK2 in proper control for cell division. Cell Cycle. 2015; 14: 802–807.

[28] Yogosawa S, Yoshida K. Tumor suppressive role for kinases phospho-rylating p53 in DNA damage-induced apoptosis. Cancer science. 2018; 109: 3376–3382.

Abstracted / indexed in

Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,200 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Chemical Abstracts Service Source Index The CAS Source Index (CASSI) Search Tool is an online resource that can quickly identify or confirm journal titles and abbreviations for publications indexed by CAS since 1907, including serial and non-serial scientific and technical publications.

Index Copernicus The Index Copernicus International (ICI) Journals database’s is an international indexation database of scientific journals. It covered international scientific journals which divided into general information, contents of individual issues, detailed bibliography (references) sections for every publication, as well as full texts of publications in the form of attached files (optional). For now, there are more than 58,000 scientific journals registered at ICI.

Geneva Foundation for Medical Education and Research The Geneva Foundation for Medical Education and Research (GFMER) is a non-profit organization established in 2002 and it works in close collaboration with the World Health Organization (WHO). The overall objectives of the Foundation are to promote and develop health education and research programs.

Scopus: CiteScore 1.0 (2022) Scopus is Elsevier's abstract and citation database launched in 2004. Scopus covers nearly 36,377 titles (22,794 active titles and 13,583 Inactive titles) from approximately 11,678 publishers, of which 34,346 are peer-reviewed journals in top-level subject fields: life sciences, social sciences, physical sciences and health sciences.

Embase Embase (often styled EMBASE for Excerpta Medica dataBASE), produced by Elsevier, is a biomedical and pharmacological database of published literature designed to support information managers and pharmacovigilance in complying with the regulatory requirements of a licensed drug.

Submission Turnaround Time