Open AccessmiR‑3613‑3p/MAP3K2/p38/caspase‑3 pathway regulates the heat‑stress‑induced apoptosis of endothelial cells
Author(s) -
Jie Liu,
Siya Xu,
Shixin Liu,
Bing-guan Chen
Publication year - 2021
Publication title -
molecular medicine reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.727
H-Index - 56
eISSN - 1791-3004
pISSN - 1791-2997
DOI - 10.3892/mmr.2021.12272
Subject(s) - propidium iodide , apoptosis , microbiology and biotechnology , p38 mitogen activated protein kinases , biology , annexin , microrna , transfection , kinase , protein kinase a , programmed cell death , cell culture , biochemistry , genetics , gene
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.