miR‑3613‑3p/MAP3K2/p38/caspase‑3 pathway regulates the heat‑stress‑induced apoptosis of endothelial cells

Abstract

Previous studies have identified microRNA (miRNA/miR)-3613-3p as a heat stress (HS)-related miRNA in endothelial cells that can lead to apoptosis. However, the mechanism underlying the miR-3613-3p-mediated apoptosis of HS-exposed endothelial cells remains unclear. In the present study, western blot analysis and reverse transcription-quantitative PCR were used to determine protein and miRNA expression levels, respectively. Annexin V-fluorescein isothiocyanate/propidium iodide staining, caspase-3 activity measurements and DNA fragmentation assays were performed to detect apoptosis. To evaluate whether mitogen-activated protein kinase kinase kinase 2 (MAP3K2) was a direct target of miR-3613-3p, a luciferase reporter assay was performed. In addition, transient transfection was used to carry out loss-and gain-of-function experiments. The results revealed that miR-3613-3p expression was reduced in human umbilical vein endothelial cells (HUVECs) following HS, which led to apoptosis. Mechanistically, following HS, a decrease in miR-3613-3p binding to the 3'-untranslated region of MAP3K2 directly upregulated its expression, and the downstream p38 and caspase-3 pathways, thereby leading to apoptosis. Taken together, the results of the present study demonstrated that HS suppressed miR-3613-3p expression, which activated the MAP3K2/p38/caspase-3 pathway, leading to the apoptosis of HUVECs. In conclusion, the miR-3613-3p/MAP3K2/p38/caspase-3 pathway may serve an indispensable role in regulating the progression of apoptosis, indicating a regulatory role of miR-3613-3p in the pathophysiology of HS-exposed endothelial cells.

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