当前位置： SCI文献检索 > INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE期刊下所有文献 > MicroRNA‑28‑3p inhibits angiotensin‑converting enzyme 2 ectodomain shedding in 293T cells treated with the spike protein of severe acute respiratory syndrome coronavirus 2 by targeting A disintegrin and metalloproteinase 17.

MicroRNA‑28‑3p inhibits angiotensin‑converting enzyme 2 ectodomain shedding in 293T cells treated with the spike protein of severe acute respiratory syndrome coronavirus 2 by targeting A disintegrin and metalloproteinase 17.

Abstract：

:Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is the virus that causes coronavirus disease 2019. Angiotensin‑converting enzyme 2 (ACE2) is the SARS‑CoV binding site and is ubiquitously expressed in endothelial cells of several organs, with the highest levels in the cardiovascular system, kidney and lungs. A disintegrin and metalloproteinase 17 (ADAM17) is involved in ectodomain shedding of ACE2. In the present study, reverse‑transcription‑quantitative PCR, transfection, TUNNEL assay, dual‑luciferase activity assay and western blotting were conducted to investigate the effects of microRNA (miR)‑28‑3p on ADAM17‑dependent shedding of the ACE2 ectodomain following treatment with the spike protein (S‑protein) of SARS‑CoV‑2. It was found that miR‑28‑3p was significantly downregulated in 293T cells treated with 100 ng/ml of S‑protein for 24 h at 37˚C, which led to upregulation of ADAM17. In addition, the expression of ADAM17 and miR‑28‑3p were negatively correlated based on Pearson's correlation test in 293T cells treated with S‑protein for 24 h. Overexpression of miR‑28‑3p and inhibition of ADAM17 regulated 293T cell viability, apoptosis and ACE2 ectodomain shedding. It was also demonstrated that ADAM17 was the target gene of miR‑28‑3p and that miR‑28‑3p negatively regulated ADAM17 expression. Notably, the inhibition of ADAM17 expression blocked the effects of miR‑28‑3p inhibitor on proliferation, apoptosis and ACE2 ectodomain shedding in 293T cells treated with S‑protein. The findings of the present study suggested that miR‑28‑3p inhibits ADAM17‑dependent ACE2 ectodomain shedding in 293T cells treated with the S‑protein of SARS‑CoV‑2, which suggested the potential therapeutic role of miR‑28‑3p mimic in the prevention and treatment of patients with SARS‑CoV‑2.

journal_name

Int J Mol Med

journal_title

International journal of molecular medicine

authors

Xu Y,Li Y

doi

10.3892/ijmm.2021.5022

keywords:

["A disintegrin and metalloproteinase 17","angiotensin‑converting enzyme 2","microRNA‑28‑3p","spike protein"]

subject

Has Abstract

pub_date

2021-10-01 00:00:00

issue

eissn

1107-3756

issn

1791-244X

pii

189

journal_volume

pub_type

杂志文章

在线工具

MicroRNA‑28‑3p inhibits angiotensin‑converting enzyme 2 ectodomain shedding in 293T cells treated with the spike protein of severe acute respiratory syndrome coronavirus 2 by targeting A disintegrin and metalloproteinase 17.