Inhibition of microRNA‑124‑3p protects against acute myocardial infarction by suppressing the apoptosis of cardiomyocytes

Abstract

The aims of the present study were to investigate the roles and underlying mechanisms of microrna-124-3p (mir-124-3p) in the progression of acute myocardial infarction (aMi). The expression of mir-124-3p was determined via reverse transcription-quantitative polymerase chain reaction (rT-qPcr). TargetScan analysis and a luciferase reporter assay were conducted to reveal the association between mir-124-3p and nuclear factor κ-light-chain-enhancer of activated B cells (nF-κB) repressing factor (nKrF). To investigate the role of mir-124-3p in aMi, a cell model of myocardial hypoxic/ischemic injury was established by subjecting H9c2 cardiac cells to hypoxia for 48 h. The viability of cells was determined using an MTT assay, and cell apoptosis was analyzed by flow cytometry. Additionally, the expression levels of inflammatory factors [tumor necrosis factor-α (TnF-α), interleukin (il)-1β and il-6] were measured via eliSa. Furthermore, gene and protein expression levels were determined by performing rT-qPcr and western blot analyses, respectively. it was revealed that the expression of miR-124-3p was significantly increased in the blood of patients with aMi and hypoxia-treated H9c2 cells. additionally, it was demonstrated that nKrF was a direct target of mir-124-3p. The hypoxia-induced decrease in the viability of H9c2 cells and increase in cell apoptosis were eliminated by the downregulation of mir-124-3p. Furthermore, hypoxia significantly increased the levels of TnF-α, il-1β and il-6, whereas mir-124-3p downregulation eliminated these effects. downregulated expression of B-cell lymphoma 2, pro-caspase 3 and pro-caspase 9 protein, and upregulated expression of cleaved caspases 3 and 9 was observed in hypoxic H9c2 cells; the altered expression of these proteins was suppressed by mir-124-3p inhibitor. additionally, mir-124-3p inhibitor suppressed the hypoxia-induced activation of the nF-κB signaling pathway in H9c2 cells. Furthermore, it was demonstrated that the various effects of mir-124-3p inhibitor on H9c2 cells were eliminated by the small interfering rna-mediated downregulation of nKrF. in conclusion, the results of the present study indicated that mir-124-3p downregulation protected against aMi via inhibition of inflammatory responses and the apoptosis of cardiomyocytes by regulating the nKrF/nF-κB pathway.

Identification and validation of senescence-related genes in circulating endothelial cells of patients with acute myocardial infarction

“…In AMI rats, inhibiting the expression of miR-124-3p can reduce apoptosis, inflammation and oxidative stress ( 50 ). In the blood of patients with AMI and hypoxia-treated H9c2 cells, the expression of miR-124-3p was significantly increased ( 51 ). Further studies have demonstrated that downregulation of miR-124-3p can inhibit inflammation and cardiomyocyte apoptosis by regulating the activated B-cell suppressor factor (NKRF)/NF-κB pathway to prevent AMI ( 51 ).…”

“…In the blood of patients with AMI and hypoxia-treated H9c2 cells, the expression of miR-124-3p was significantly increased ( 51 ). Further studies have demonstrated that downregulation of miR-124-3p can inhibit inflammation and cardiomyocyte apoptosis by regulating the activated B-cell suppressor factor (NKRF)/NF-κB pathway to prevent AMI ( 51 ). Several miRNAs such as miR-17-3p, miR-34a, and miR-22 are reported to be involved in the pathophysiology of cell senescence ( 52 ).…”

Activation of PTEN/P13K/AKT Signaling Pathway by miRNA-124-3p-Loaded Nanoparticles to Regulate Oxidative Stress Attenuates Cardiomyocyte Regulation and Myocardial Injury

“…As a member of the miRNA family, miRNA-124-3p correlates with the proliferation and apoptosis of cells [ 24 ]. Multiple researches have indicated the great importance of miR-124-3p in cardiovascular diseases [ 25 ]. The PTEN gene is the first novel tumor suppressor gene with specific phosphatase activity that was cloned in 1997 and can effectively inhibit the growth of tumor cells [ 26 ].…”

Long-term culture of patient-derived cardiac organoids recapitulated Duchenne muscular dystrophy cardiomyopathy and disease progression

“…Similarly, the hsa-mir-26a/b-5p was highly expressed in cardiac hypertrophy ( Tang et al, 2020 ) and promoted myocardial infarction-induced cell death ( Jung et al, 2021 ), yet overexpression of miR-26a/b attenuated cardiac fibrosis ( Tang et al, 2017 ; Wang et al, 2019 ) and alleviated cardiac hypertrophy and dysfunction ( Shi et al, 2021 ). Lastly, the hsa-mir-124-3p was reported to promote cardiac fibroblast activation and proliferation ( Zhu et al, 2021 ), and its inhibition protects against acute myocardial infarction by suppressing cardiomyocyte apoptosis ( Hu et al, 2019 ). Based on the duality effects of these miRNAs, the potential of these miRNAs as therapeutic targets for DMD-related cardiomyopathy need to be assessed carefully.…”