PMID- 34037903
OWN - NLM
STAT- MEDLINE
DCOM- 20211018
LR  - 20240226
IS  - 1573-6903 (Electronic)
IS  - 0364-3190 (Linking)
VI  - 46
IP  - 8
DP  - 2021 Aug
TI  - Knockdown of XIST Attenuates Cerebral Ischemia/Reperfusion Injury Through 
      Regulation of miR-362/ROCK2 Axis.
PG  - 2167-2180
LID - 10.1007/s11064-021-03354-6 [doi]
AB  - Long non-coding RNAs (lncRNAs) are considered as critical regulators in the 
      pathogenesis of cerebral ischemia. In this present study, we aimed to investigate 
      the impact and underlying mechanism of lncRNA X-inactive specific transcript 
      (XIST) in cerebral ischemia/reperfusion (I/R) injury. An oxygen-glucose 
      deprivation/reperfusion (OGD/R) model in PC12 cells was applied to mimic cerebral 
      I/R injury in vitro and middle cerebral artery occlusion/reperfusion (MCAO/R) 
      model was performed in mice to mimic cerebral I/R injury in vivo. Real-time PCR, 
      fluorescence in situ hybridization (FISH) assay, and western blotting assay were 
      carried out to detect the expression levels of XIST, miR-362, and Rho-related 
      coiled-coil containing protein kinase 2 (ROCK2). The functional experiments were 
      measured by CCK-8 assay, immumofluorescence assay, ELISA assay, TUNEL, and TTC 
      staining. Results displayed that XIST was elevated in PC12 cells with OGD/R, as 
      well as in the ischemic penumbra of mice with MCAO/R. In vitro, knockdown of XIST 
      facilitated cell survival, inhibited apoptosis, and alleviated inflammation 
      injury in OGDR PC12 cells. In vivo, inhibition of XIST remarkably reduced the 
      neurological impairments, promoted neuron proliferation, and suppressed apoptosis 
      in MCAO mice. Mechanistically, XIST acted as a competing endogenous RNA of 
      miR-362 to regulate the downstream gene ROCK2. In conclusion, depletion of XIST 
      attenuated I/R-induced neurological impairment and inflammatory response via the 
      miR-362/ROCK2 axis. These findings offer a potential novel strategy for ischemic 
      stroke therapy.
FAU - Wang, Jingtao
AU  - Wang J
AD  - Department of Neurology, The First Affiliated Hospital of Zhengzhou University, 
      No. 1, Jianshe East Road, Erqi District, Zhengzhou, 450052, Henan, China.
FAU - Fu, Zhenqiang
AU  - Fu Z
AD  - Department of Neurology, The First Affiliated Hospital of Zhengzhou University, 
      No. 1, Jianshe East Road, Erqi District, Zhengzhou, 450052, Henan, China.
FAU - Wang, Menghan
AU  - Wang M
AD  - Department of Neurology, The First Affiliated Hospital of Zhengzhou University, 
      No. 1, Jianshe East Road, Erqi District, Zhengzhou, 450052, Henan, China.
FAU - Lu, Jingjing
AU  - Lu J
AD  - Department of Neurology, The First Affiliated Hospital of Zhengzhou University, 
      No. 1, Jianshe East Road, Erqi District, Zhengzhou, 450052, Henan, China.
FAU - Yang, Hecheng
AU  - Yang H
AD  - Department of Neurology, The First Affiliated Hospital of Zhengzhou University, 
      No. 1, Jianshe East Road, Erqi District, Zhengzhou, 450052, Henan, China.
FAU - Lu, Hong
AU  - Lu H
AUID- ORCID: 0000-0001-8508-7616
AD  - Department of Neurology, The First Affiliated Hospital of Zhengzhou University, 
      No. 1, Jianshe East Road, Erqi District, Zhengzhou, 450052, Henan, China. 
      honglu6666@yeah.net.
LA  - eng
PT  - Journal Article
DEP - 20210526
PL  - United States
TA  - Neurochem Res
JT  - Neurochemical research
JID - 7613461
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (XIST non-coding RNA)
RN  - EC 2.7.11.1 (Rock2 protein, mouse)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
RN  - IY9XDZ35W2 (Glucose)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Cell Hypoxia/physiology
MH  - Gene Knockdown Techniques
MH  - Glucose/deficiency
MH  - Infarction, Middle Cerebral Artery/*metabolism
MH  - Inflammation/metabolism
MH  - Male
MH  - Mice, Inbred C57BL
MH  - MicroRNAs/*metabolism
MH  - Oxygen/metabolism
MH  - PC12 Cells
MH  - RNA, Long Noncoding/genetics/*metabolism
MH  - Rats
MH  - Reperfusion Injury/*metabolism
MH  - rho-Associated Kinases/*metabolism
MH  - Mice
OTO - NOTNLM
OT  - Cerebral ischemia/reperfusion
OT  - ROCK2
OT  - XIST
OT  - miR-362
EDAT- 2021/05/27 06:00
MHDA- 2021/10/21 06:00
CRDT- 2021/05/26 12:40
PHST- 2021/02/02 00:00 [received]
PHST- 2021/05/13 00:00 [accepted]
PHST- 2021/05/12 00:00 [revised]
PHST- 2021/05/27 06:00 [pubmed]
PHST- 2021/10/21 06:00 [medline]
PHST- 2021/05/26 12:40 [entrez]
AID - 10.1007/s11064-021-03354-6 [pii]
AID - 10.1007/s11064-021-03354-6 [doi]
PST - ppublish
SO  - Neurochem Res. 2021 Aug;46(8):2167-2180. doi: 10.1007/s11064-021-03354-6. Epub 
      2021 May 26.