MiR-124 Promotes Apoptosis and Inhibits the Proliferation of Vessel Endothelial Cells Through P38/MAPK and PI3K/AKT Pathways, Making It a Potential Mechanism of Vessel Endothelial Injury in Acute Myocardial Infarction

Overview

Journal Exp Ther Med

Specialty Pathology

Date 2021 Oct 15

PMID 34650631

Citations 4

Authors

Weimin Ma

Xin Zhang

Yang Liu

Affiliations

Soon will be listed here.

Abstract

Due to its rapid onset and high rates of fatality, acute myocardial infarction (AMI) has long been one of the most fatal diseases among all types of heart diseases. Therefore, intensive research efforts have been focused on understanding AMI's potential pathogenesis to seek effective treatment options. In the present study, 20 peripheral blood samples were collected from patients with AMI, after which reverse transcription-quantitative PCR analysis revealed that microRNA (miR)-124 levels in the peripheral blood of patients with AMI was significantly elevated compared with that in the control group. , a model using pcDNA3.1-miR-124 transfected human umbilical vein endothelial cells (HUVECs) indicated that overexpression of miR-124 could significantly promote the apoptosis and suppress the proliferation of HUVECs using flow cytometry, TUNEL assay and Cell Counting Kit-8 assays. Based on the present findings, RNA samples of HUVECs overexpressing miR-124 was extracted and sequenced to explore the gene expression profile after miR-124 overexpression. Gene Set Enrichment Analysis (GSEA) analysis revealed that the downregulated genes were mainly enriched in signaling pathways, such as PI3K-AKT, whilst the upregulated genes were mainly enriched in metabolism-related signaling pathways, such as the metabolism of xenobiotics by cytochrome P450 pathway. Additionally, Rideogram software was used to determine the chromosomal localization of the differentially expressed genes. The results demonstrated that they were distributed on all chromosomes except for chromosome Y. In addition, characteristic profiles of the differentially expressed genes caused by miR-124 overexpression were analyzed using Connectivity Map. In total, two medicines, anisomycin and sanguinarine, which function as p38/MAPK signaling agonists that can inhibit angiogenesis, presented with the highest enrichment scores. Together with the GSEA results, which indicated that the differentially expressed genes were mainly enriched in the angiogenesis-inhibiting PI3K/AKT signaling pathway, the present study reported that high expression of miR-124 was negatively associated with patients with AMI, promoting the apoptosis and suppressing the proliferation of vessel endothelial cells.

Citing Articles

Protective role of Tongxinluo in mitigating myocardial fibrosis in mice with acute myocardial infarction via neuregulin-1 upregulation and Inhibition of endothelium-interstitial transition.

Li Z, Yin Y, Wei Y, Liu Y, Han N, Wang X J Mol Histol. 2025; 56(2):103.

PMID: 40063284 PMC: 11893718. DOI: 10.1007/s10735-025-10378-7.

Sensitive fluorescence detection of miRNA-124 in cardiomyocytes under oxidative stress using a nucleic acid probe.

Li S, Pei X, Liu X, Wang S, Xu W, Wang J Heliyon. 2024; 10(13):e33588.

PMID: 39040278 PMC: 11260977. DOI: 10.1016/j.heliyon.2024.e33588.

MiR-497-5p regulates ox-LDL-induced dysfunction in vascular endothelial cells by targeting VEGFA/p38/MAPK pathway in atherosclerosis.

Lu W, Wan G, Zhu H, Zhu T, Zhang X Heliyon. 2024; 10(7):e28887.

PMID: 38601630 PMC: 11004747. DOI: 10.1016/j.heliyon.2024.e28887.

Response surface optimization of a cardioprotective compound through pharmacosomal drug delivery system: in vivo bioavailability and cardioprotective activity potential.

Dawoud M, Zaafan M, Saleh S, Mannaa I, Sweed N Drug Deliv Transl Res. 2023; 13(9):2315-2339.

PMID: 37017879 PMC: 10382421. DOI: 10.1007/s13346-023-01315-w.

The Role of Epithelial Mesenchymal Transition (EMT) in Pathogenesis of Cardiotoxicity: Diagnostic & Prognostic Approach.

Kardooni A, Bahrampour A, Golmohammadi S, Jalili A, Alishahi M Mol Biotechnol. 2023; 65(9):1403-1413.

PMID: 36847962 DOI: 10.1007/s12033-023-00697-z.

References

Chen J, Zacharek A, Cui X, Shehadah A, Jiang H, Roberts C . Treatment of stroke with a synthetic liver X receptor agonist, TO901317, promotes synaptic plasticity and axonal regeneration in mice. J Cereb Blood Flow Metab. 2009; 30(1):102-9. PMC: 2804900. DOI: 10.1038/jcbfm.2009.187. View

Cheng S, Zhang X, Feng Q, Chen J, Shen L, Yu P . Astragaloside IV exerts angiogenesis and cardioprotection after myocardial infarction via regulating PTEN/PI3K/Akt signaling pathway. Life Sci. 2019; 227:82-93. DOI: 10.1016/j.lfs.2019.04.040. View

Su T, Shao X, Zhang X, Yang C, Shao X . Value of circulating miRNA-1 detected within 3 h after the onset of acute chest pain in the diagnosis and prognosis of acute myocardial infarction. Int J Cardiol. 2019; 307:146-151. DOI: 10.1016/j.ijcard.2019.09.050. View

Yang J, Shamji A, Matchacheep S, Schreiber S . Identification of a small-molecule inhibitor of class Ia PI3Ks with cell-based screening. Chem Biol. 2007; 14(4):371-7. DOI: 10.1016/j.chembiol.2007.02.004. View

Guo M, Guo L, Weng Y . Implication of peripheral blood miRNA-124 in predicting acute myocardial infarction. Eur Rev Med Pharmacol Sci. 2017; 21(5):1054-1059. View

Lei Z, Klasson T, Brandt M, van de Hoek G, Logister I, Cheng C . Control of Angiogenesis via a VHL/miR-212/132 Axis. Cells. 2020; 9(4). PMC: 7226144. DOI: 10.3390/cells9041017. View

Zhu Y, Liu X, Zhao P, Zhao H, Gao W, Wang L . Celastrol Suppresses Glioma Vasculogenic Mimicry Formation and Angiogenesis by Blocking the PI3K/Akt/mTOR Signaling Pathway. Front Pharmacol. 2020; 11:25. PMC: 7025498. DOI: 10.3389/fphar.2020.00025. View

Blankenberg D, Gordon A, Von Kuster G, Coraor N, Taylor J, Nekrutenko A . Manipulation of FASTQ data with Galaxy. Bioinformatics. 2010; 26(14):1783-5. PMC: 2894519. DOI: 10.1093/bioinformatics/btq281. View

Makeyev E, Zhang J, Carrasco M, Maniatis T . The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Mol Cell. 2007; 27(3):435-48. PMC: 3139456. DOI: 10.1016/j.molcel.2007.07.015. View

10.

Bartel D . MicroRNAs: target recognition and regulatory functions. Cell. 2009; 136(2):215-33. PMC: 3794896. DOI: 10.1016/j.cell.2009.01.002. View

11.

Han F, Chen Q, Su J, Zheng A, Chen K, Sun S . MicroRNA-124 regulates cardiomyocyte apoptosis and myocardial infarction through targeting Dhcr24. J Mol Cell Cardiol. 2019; 132:178-188. DOI: 10.1016/j.yjmcc.2019.05.007. View

12.

Martini M, De Santis M, Braccini L, Gulluni F, Hirsch E . PI3K/AKT signaling pathway and cancer: an updated review. Ann Med. 2014; 46(6):372-83. DOI: 10.3109/07853890.2014.912836. View

13.

Chen X, Wang R, Chen W, Lai L, Li Z . Decoy receptor-3 regulates inflammation and apoptosis via PI3K/AKT signaling pathway in coronary heart disease. Exp Ther Med. 2019; 17(4):2614-2622. PMC: 6425242. DOI: 10.3892/etm.2019.7222. View

14.

Wang X, Chen L, Zhao X, Xiao L, Yi S, Kong Y . A cathelicidin-related antimicrobial peptide suppresses cardiac hypertrophy induced by pressure overload by regulating IGFR1/PI3K/AKT and TLR9/AMPKα. Cell Death Dis. 2020; 11(2):96. PMC: 7005284. DOI: 10.1038/s41419-020-2296-4. View

15.

Brughera M, Scampini G, Newman A, Castellino S, Sammartini U, Mazue G . Overview of toxicological data on rifabutin. Exp Toxicol Pathol. 1995; 47(1):1-9. DOI: 10.1016/s0940-2993(11)80273-3. View

16.

Hao Z, Lv D, Ge Y, Shi J, Weijers D, Yu G . : drawing SVG graphics to visualize and map genome-wide data on the idiograms. PeerJ Comput Sci. 2021; 6:e251. PMC: 7924719. DOI: 10.7717/peerj-cs.251. View

17.

Gimenez V, de Las Heras N, Ferder L, Lahera V, Reiter R, Manucha W . Potential Effects of Melatonin and Micronutrients on Mitochondrial Dysfunction during a Cytokine Storm Typical of Oxidative/Inflammatory Diseases. Diseases. 2021; 9(2). PMC: 8167770. DOI: 10.3390/diseases9020030. View

18.

Pimentel H, Bray N, Puente S, Melsted P, Pachter L . Differential analysis of RNA-seq incorporating quantification uncertainty. Nat Methods. 2017; 14(7):687-690. DOI: 10.1038/nmeth.4324. View

19.

Chai W, Wu Y, Li G, Cao W, Yang Z, Liu Z . Activation of p38 mitogen-activated protein kinase abolishes insulin-mediated myocardial protection against ischemia-reperfusion injury. Am J Physiol Endocrinol Metab. 2007; 294(1):E183-9. DOI: 10.1152/ajpendo.00571.2007. View

20.

Hao Q, Zhang F, Wang Y, Li Y, Qi X . Cardiac Contractility Modulation Attenuates Chronic Heart Failure in a Rabbit Model via the PI3K/AKT Pathway. Biomed Res Int. 2020; 2020:1625362. PMC: 6973194. DOI: 10.1155/2020/1625362. View