miR‑126‑5p regulates H9c2 cell proliferation and apoptosis under hypoxic conditions by targeting IL‑17A

Abstract

Accumulating evidence has indicated that microRNAs (miRNAs/miRs) regulate the occurrence and development of various diseases, including diabetes, osteoporosis and cardiovascular conditions. However, the role of miRNAs in acute myocardial infarction (AMI) is not completely understood. The present study aimed to evaluate the therapeutic efficacy and mechanisms underlying the effects of miR-126-5p on H9c2 cell proliferation and apoptosis by targeting interleukin (IL)-17A. A total of 40 patients with AMI and 40 healthy volunteers were recruited in the present study and the expression levels of serum miR-126-5p and IL-17A were determined. Following confirmation that IL-17A was a target of miR-126-5p via a dual-luciferase reporter assay, H9c2 cells were exposed to hypoxic conditions. H9c2 cell viability and apoptosis were subsequently assessed. Additionally, the protein expression levels of apoptosis-associated proteins were detected following transfection. Compared with healthy individuals, miR-126-5p expression was significantly decreased in the serum samples of patients with AMI, whereas IL-17A, the target of miR-126-5p, was significantly increased. Following hypoxic treatment, miR-126-5p overexpression enhanced H9c2 cell viability compared with the NC group, which was subsequently reversed following co-transfection with pcDNA3.1-IL-17A. Additionally, the results indicated that hypoxia-induced H9c2 cell apoptosis was significantly reduced following transfection with miR-126-5p mimics via the PI3K/AKT signaling pathway compared with the NC group. The present study indicated that miR-126-5p may serve as a novel miRNA that regulates H9c2 cell viability and apoptosis by targeting IL-17A under hypoxic conditions. Therefore, miR-126-5p may serve as a crucial biomarker for the diagnosis of AMI.

"Regulatory Roles for miR-126 in Inflammatory Response and Programmed Death of Cardiac Myocytes Driven by Acidosis During Simulated Ischemia"

“…The findings are consistent with our previous reports that hypoxia with concurrent acidosis, but not hypoxia alone confers lethal cardiac myocyte injury through BH3-only pathways [9][10][11]35,36,50]. The results are also consistent with our previous report, and that of others that miR-126, while generally considered to be endothelial-specific is induced by hypoxia in non-endothelial cells including cardiac myocytes and regulates pro-survival kinases and inflammatory cytokines [32,51]. Acidosis appears to be the critical regulator of miR-126 expression in this model and the implications of the studies extend beyond those of ischemic cardiac injury to other conditions of acidosis including rapidly growing solid tumors.…”

“…MiR-126 is enriched in endothelial cells (EC) and EC progenitors, and has been assigned essential roles in cardiac developmental as well as in the recovery of the heart from injury by activating survival kinases ERK1/2 and Akt and increasing proangiogenic signaling [29][30][31]. Roles for mirR-126 have also been described in the regulation of cardiac myocyte proliferation and inflammation, including Interleukins in non-endothelial H 9 c 2 cells [32]. Aberrant expression of miR-126 associated with vascular pathologies including but not limited to cancers, diabetes and ocular disease has revealed roles in a range of biological processes including apoptosis, autophagy, pathological angiogenesis, cell migration and proliferation [33,34].…”

MiR-126-HMGB1-HIF-1 Axis Regulates Endothelial Cell Inflammation during Exposure to Hypoxia-Acidosis

“…Although miR-126 has been widely studied in the context of cellular hypoxia [22][23][24][25][26][27], its role in ECs subjected to chronic ischemic and/or acidotic conditions is relatively unexplored. HIF-1α has been shown to induce the miR-126 expression in a number of cell types including cultured human umbilical vein endothelial cells, and other studies have described positive feedback loop regulation between HIF-1α and miR-126 [26,28,29].…”

MicroRNAs serve as prediction and treatment-response biomarkers of attention-deficit/hyperactivity disorder and promote the differentiation of neuronal cells by repressing the apoptosis pathway

“…Apoptosis refers to an active, programmed process of autonomous cellular dismantling, and necrosis is described as unplanned cell death resulting from environmental perturbations in the inflammatory process [ 54 ]. A previous in vitro study indicated that miR-126-5p may regulate H9c2 cell viability and apoptosis by targeting IL-17A under hypoxic conditions [ 55 ]. Another study revealed that overexpressing miR-140-3p may exert cytoprotective effects by alleviating inflammation and oxidative stress and reducing cell apoptosis in OGD/R [ 56 ].…”