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

Liu,Jie; Xu,Siya; Liu,Shixin; Chen,Bingguan

doi:10.3892/mmr.2021.12272

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

Authors:
- Jie Liu
- Siya Xu
- Shixin Liu
- Bingguan Chen
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Affiliations: Department of Intensive Care Unit, Hefei Boe Hospital Co., Ltd., Hefei, Anhui 230011, P.R. China, Department of Emergency, Central Theater General Hospital of The People's Liberation Army of China, Wuhan, Hubei 430070, P.R. China, Department of General Surgery, Hefei Boe Hospital Co., Ltd., Hefei, Anhui 230011, P.R. China
Published online on: July 6, 2021 https://doi.org/10.3892/mmr.2021.12272
Article Number: 633
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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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