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

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.