PMID- 32048632
OWN - NLM
STAT- MEDLINE
DCOM- 20201214
LR  - 20221222
IS  - 1643-3750 (Electronic)
IS  - 1234-1010 (Print)
IS  - 1234-1010 (Linking)
VI  - 26
DP  - 2020 Feb 2
TI  - Downregulation of MiR-218-5p Protects Against Oxygen-Glucose 
      Deprivation/Reperfusion-Induced Injuries of PC12 Cells via Upregulating N-myc 
      Downstream Regulated Gene 4 (NDRG4).
PG  - e920101
LID - 10.12659/MSM.920101 [doi]
AB  - <strong>BACKGROUND</strong> Cerebral ischemia is a major player of acute ischemic 
      stroke (AIS) and mainly caused by blood vessels obstruction-induced reduced blood 
      flow. Furthermore, miR-218-5p level was elevated in patients with AIS compared 
      with controls. The present study investigated the biochemical mechanisms 
      underlying the role of miR-218-5p in AIS in vitro. <strong>MATERIAL AND 
      METHODS</strong> PC12 cells were chosen to establish oxidative-glucose 
      deprivation/re-oxygenation (OGD/R) injury model. The interaction between 
      miR-218-5p and N-myc downstream regulated gene 4 (NDRG4) was evaluated by 
      Luciferase reporter assay. The levels of NDRG4, endothelial nitric oxide synthase 
      (eNOS) and protein related to cell apoptosis were quantitatively analyzed with 
      real-time quantitative polymerase chain reaction (RT-qPCR) or western blotting. 
      Inflammatory cytokines, myeloperoxidase (MPO) and oxidative stress status were 
      measured using specific commercial assay kits. Further, the cells apoptosis was 
      analyzed with flow cytometry assay. <strong>RESULTS</strong> MiR-218-5p level was 
      notably increased in OGD/R injured PC12 cells and directly targeted NDRG4. 
      MiR-218-5p inhibitor significantly inhibited inflammatory cytokines release, 
      including tumor necrosis factor-alpha (TNF-alpha), interleukin-1ss (IL-1ss), and 
      monocyte chemotactic protein 1 (MCP-1). In addition, miR-218-5p downregulation 
      ameliorated nitric oxide (NO) and eNOS levels and suppressed the inducible nitric 
      oxide synthase (iNOS) expression and cell apoptosis. However, NDRG4 silencing 
      abolished all corrective effects of miR-218-5p inhibitor in OGD/R injured PC12 
      cells. <strong>CONCLUSIONS</strong> Downregulation of miR-218-5p protect against 
      OGDR-induced injuries of PC12 cells through reducing inflammatory cytokines 
      secretion, oxidative stress status, apoptosis rate and maintenance of 
      endovascular homeostasis via upregulating NDRG4. MiR-218-5p may serve as a novel 
      effective biomarker to monitor AIS progression.
FAU - Zhu, Huiying
AU  - Zhu H
AD  - Department of Neurology, Wuhan First Hospital, Wuhan, Hubei, China (mainland).
FAU - Wang, Xiaojing
AU  - Wang X
AD  - Department of Neurology, Hospital, Baicheng, Jilin, China (mainland).
FAU - Chen, Shaoyuan
AU  - Chen S
AD  - Department of Neurology, Hospital, Baicheng, Jilin, China (mainland).
LA  - eng
PT  - Journal Article
DEP - 20200202
PL  - United States
TA  - Med Sci Monit
JT  - Medical science monitor : international medical journal of experimental and 
      clinical research
JID - 9609063
RN  - 0 (Biomarkers)
RN  - 0 (Culture Media)
RN  - 0 (MIRN218 microRNA, rat)
RN  - 0 (MicroRNAs)
RN  - 0 (Muscle Proteins)
RN  - 0 (Ndrg4 protein, rat)
RN  - 0 (Nerve Tissue Proteins)
RN  - IY9XDZ35W2 (Glucose)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects/genetics
MH  - Biomarkers/metabolism
MH  - Culture Media/metabolism
MH  - Down-Regulation
MH  - Glucose/metabolism
MH  - Humans
MH  - Ischemic Stroke/*complications/genetics/pathology
MH  - MicroRNAs/antagonists & inhibitors/*metabolism
MH  - Muscle Proteins/*genetics
MH  - Nerve Tissue Proteins/*genetics
MH  - Oxidative Stress/drug effects/genetics
MH  - Oxygen/metabolism
MH  - PC12 Cells
MH  - Rats
MH  - Reperfusion Injury/*genetics/pathology
MH  - Up-Regulation
PMC - PMC7009718
COIS- Conflict of interest None.
EDAT- 2020/02/13 06:00
MHDA- 2020/12/15 06:00
PMCR- 2020/02/02
CRDT- 2020/02/13 06:00
PHST- 2020/02/13 06:00 [entrez]
PHST- 2020/02/13 06:00 [pubmed]
PHST- 2020/12/15 06:00 [medline]
PHST- 2020/02/02 00:00 [pmc-release]
AID - 920101 [pii]
AID - 10.12659/MSM.920101 [doi]
PST - epublish
SO  - Med Sci Monit. 2020 Feb 2;26:e920101. doi: 10.12659/MSM.920101.