PMID- 34414454
OWN - NLM
STAT- MEDLINE
DCOM- 20210906
LR  - 20210918
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Print)
IS  - 1107-3756 (Linking)
VI  - 48
IP  - 4
DP  - 2021 Oct
TI  - 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.
LID - 189 [pii]
LID - 10.3892/ijmm.2021.5022 [doi]
AB  - 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.
FAU - Xu, Yun
AU  - Xu Y
AD  - Department of Infectious Diseases, The Second Xiangya Hospital of Central South 
      University, Changsha, Hunan 410011, P.R. China.
FAU - Li, Yi
AU  - Li Y
AD  - Department of Infectious Diseases, The Second Xiangya Hospital of Central South 
      University, Changsha, Hunan 410011, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20210820
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (MIRN28 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - EC 3.4.17.23 (ACE2 protein, human)
RN  - EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
RN  - EC 3.4.24.86 (ADAM17 Protein)
RN  - EC 3.4.24.86 (ADAM17 protein, human)
SB  - IM
MH  - ADAM17 Protein/*metabolism
MH  - Angiotensin-Converting Enzyme 2/*chemistry
MH  - Apoptosis
MH  - COVID-19/*immunology/virology
MH  - Cell Proliferation
MH  - Cell Survival
MH  - *Gene Expression Profiling
MH  - Gene Expression Regulation, Viral
MH  - HEK293 Cells
MH  - Humans
MH  - MicroRNAs/antagonists & inhibitors/*physiology
MH  - Protein Domains
PMC - PMC8416148
OTO - NOTNLM
OT  - A disintegrin and metalloproteinase 17
OT  - angiotensin‑converting enzyme 2
OT  - microRNA‑28‑3p
OT  - spike protein
COIS- The authors declare that they have no competing interests.
EDAT- 2021/08/21 06:00
MHDA- 2021/09/07 06:00
PMCR- 2021/08/16
CRDT- 2021/08/20 07:14
PHST- 2020/09/28 00:00 [received]
PHST- 2021/07/09 00:00 [accepted]
PHST- 2021/08/20 07:14 [entrez]
PHST- 2021/08/21 06:00 [pubmed]
PHST- 2021/09/07 06:00 [medline]
PHST- 2021/08/16 00:00 [pmc-release]
AID - 189 [pii]
AID - ijmm-48-04-05022 [pii]
AID - 10.3892/ijmm.2021.5022 [doi]
PST - ppublish
SO  - Int J Mol Med. 2021 Oct;48(4):189. doi: 10.3892/ijmm.2021.5022. Epub 2021 Aug 20.