PMID- 35927544
OWN - NLM
STAT- MEDLINE
DCOM- 20220913
LR  - 20220920
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Linking)
VI  - 59
IP  - 10
DP  - 2022 Oct
TI  - miR-383-5p Regulated by the Transcription Factor CTCF Affects Neuronal Impairment 
      in Cerebral Ischemia by Mediating Deacetylase HDAC9 Activity.
PG  - 6307-6320
LID - 10.1007/s12035-022-02840-4 [doi]
AB  - Stroke, the leading cause of long-term disability worldwide, is caused by the 
      blockage or hemorage of cerebral arteries. The resultant cerebral ischemia causes 
      local neuronal death and brain injury. Histone deacetylase 9 (HDAC9) has been 
      reported to be elevated in ischemic brain injury, but its mechanism in stroke is 
      still enigmatic. The present study aimed to unveil the manner of regulation of 
      HDAC9 expression and the effect of HDAC9 activation on neuronal function in 
      cerebral ischemia. MicroRNAs (miRNAs) targeting HDAC9 were predicted utilizing 
      bioinformatics analysis. We then constructed the oxygen glucose deprivation (OGD) 
      cell model and the middle cerebral artery occlusion (MCAO) rat model, and 
      elucidated the expression of CCCTC binding factor (CTCF)/miR-383-5p/HDAC9. 
      Targeting between miR-383-5p and HDAC9 was verified by dual-luciferase reporter 
      assay and RNAi. After conducting an overexpression/knockdown assay, we assessed 
      neuronal impairment and brain injury. We found that CTCF inhibited miR-383-5p 
      expression via its enrichment in the promoter region of miR-383-5p, whereas the 
      miR-383-5p targeted and inhibited HDAC9 expression. In the OGD model and the MCAO 
      model, we confirmed that elevation of HDAC9 regulated by the 
      CTCF/miR-383-5p/HDAC9 pathway mediated apoptosis induced by endoplasmic reticulum 
      stress, while reduction of HDAC9 alleviated apoptosis and the symptoms of 
      cerebral infarction in MCAO rats. Thus, the CTCF/miR-383-5p/HDAC9 pathway may 
      present a target for drug development against ischemic brain injury.
CI  - (c) 2022. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Shen, Jun
AU  - Shen J
AD  - Department of Neurology, The First Affiliated Hospital of Soochow University, 
      No.188, Shizi Road, Suzhou, 215006, People's Republic of China.
AD  - Department of Neurology, The Affiliated Huai'an Hospital of Xuzhou Medical 
      University & The Second People's Hospital of Huai'an, Huai'an, 223302, People's 
      Republic of China.
FAU - Han, Qiu
AU  - Han Q
AD  - Department of Neurology, Huai'an First People's Hospital & The Affiliated Huai'an 
      No. 1 People's Hospital of Nanjing Medical University, Huai'an, 223300, People's 
      Republic of China.
FAU - Li, Wangjun
AU  - Li W
AD  - Department of Neurology, Changshu No. 2 People's Hospital (The 5th Clinical 
      Medical College of Yangzhou University), Changshu, 215501, People's Republic of 
      China.
FAU - Chen, Xiaochang
AU  - Chen X
AD  - Department of Neurology, Hongze Huai'an District People's Hospital, No. 102, 
      Huai'an, 223100, People's Republic of China. Xiaolulu545@163.com.
FAU - Lu, Jingmin
AU  - Lu J
AD  - Department of Neurology, The Affiliated Huai'an Hospital of Xuzhou Medical 
      University & The Second People's Hospital of Huai'an, Huai'an, 223302, People's 
      Republic of China.
FAU - Zheng, Jinyu
AU  - Zheng J
AD  - Department of Neurosurgery, The Affiliated Huai'an Hospital of Xuzhou Medical 
      University & The Second People's Hospital of Huai'an, Huai'an, 223302, People's 
      Republic of China.
FAU - Xue, Shouru
AU  - Xue S
AUID- ORCID: 0000-0002-3536-909X
AD  - Department of Neurology, The First Affiliated Hospital of Soochow University, 
      No.188, Shizi Road, Suzhou, 215006, People's Republic of China. 
      xueshouru@suda.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20220804
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (CCCTC-Binding Factor)
RN  - 0 (Ctcf protein, rat)
RN  - 0 (MIRN383 microRNA, rat)
RN  - 0 (MicroRNAs)
RN  - 0 (Transcription Factors)
RN  - EC 3.5.1.98 (HDAC9 protein, rat)
RN  - EC 3.5.1.98 (Histone Deacetylases)
RN  - IY9XDZ35W2 (Glucose)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - *Brain Injuries
MH  - *Brain Ischemia/genetics/metabolism
MH  - CCCTC-Binding Factor
MH  - Glucose/metabolism
MH  - Histone Deacetylases
MH  - Infarction, Middle Cerebral Artery/complications/metabolism
MH  - *MicroRNAs/genetics/metabolism
MH  - Oxygen
MH  - Rats
MH  - *Reperfusion Injury/metabolism
MH  - *Stroke/metabolism
MH  - Transcription Factors
OTO - NOTNLM
OT  - Apoptosis
OT  - CTCF
OT  - Cerebral ischemia
OT  - Endoplasmic reticulum stress
OT  - HDAC9
OT  - Neuronal impairment
OT  - miR-383-5p
EDAT- 2022/08/05 06:00
MHDA- 2022/09/14 06:00
CRDT- 2022/08/04 23:37
PHST- 2021/02/02 00:00 [received]
PHST- 2022/04/01 00:00 [accepted]
PHST- 2022/08/05 06:00 [pubmed]
PHST- 2022/09/14 06:00 [medline]
PHST- 2022/08/04 23:37 [entrez]
AID - 10.1007/s12035-022-02840-4 [pii]
AID - 10.1007/s12035-022-02840-4 [doi]
PST - ppublish
SO  - Mol Neurobiol. 2022 Oct;59(10):6307-6320. doi: 10.1007/s12035-022-02840-4. Epub 
      2022 Aug 4.