MicroRNA283p inhibits angiotensinconverting 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.
Int J Mol Med
; 48(4)2021 Oct.
Article
in English
| MEDLINE | ID: covidwho-1367949
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARSCoV2) is the virus that causes coronavirus disease 2019. Angiotensinconverting enzyme 2 (ACE2) is the SARSCoV 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, reversetranscriptionquantitative PCR, transfection, TUNNEL assay, dualluciferase activity assay and western blotting were conducted to investigate the effects of microRNA (miR)283p on ADAM17dependent shedding of the ACE2 ectodomain following treatment with the spike protein (Sprotein) of SARSCoV2. It was found that miR283p was significantly downregulated in 293T cells treated with 100 ng/ml of Sprotein for 24 h at 37ËC, which led to upregulation of ADAM17. In addition, the expression of ADAM17 and miR283p were negatively correlated based on Pearson's correlation test in 293T cells treated with Sprotein for 24 h. Overexpression of miR283p and inhibition of ADAM17 regulated 293T cell viability, apoptosis and ACE2 ectodomain shedding. It was also demonstrated that ADAM17 was the target gene of miR283p and that miR283p negatively regulated ADAM17 expression. Notably, the inhibition of ADAM17 expression blocked the effects of miR283p inhibitor on proliferation, apoptosis and ACE2 ectodomain shedding in 293T cells treated with Sprotein. The findings of the present study suggested that miR283p inhibits ADAM17dependent ACE2 ectodomain shedding in 293T cells treated with the Sprotein of SARSCoV2, which suggested the potential therapeutic role of miR283p mimic in the prevention and treatment of patients with SARSCoV2.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Gene Expression Profiling
/
MicroRNAs
/
ADAM17 Protein
/
Angiotensin-Converting Enzyme 2
/
COVID-19
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal subject:
Molecular Biology
/
Genetics, Medical
Year:
2021
Document Type:
Article
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