PMID- 33833132
OWN - NLM
STAT- MEDLINE
DCOM- 20210802
LR  - 20211204
IS  - 1945-4589 (Electronic)
IS  - 1945-4589 (Linking)
VI  - 13
IP  - 8
DP  - 2021 Apr 4
TI  - lncRNA C2dat2 facilitates autophagy and apoptosis via the miR-30d-5p/DDIT4/mTOR 
      axis in cerebral ischemia-reperfusion injury.
PG  - 11315-11335
LID - 10.18632/aging.202824 [doi]
AB  - Cerebral ischemia-reperfusion injury (CIRI) is an important pathophysiological 
      process of ischemic stroke associated with various physiological and pathological 
      processes, including autophagy and apoptosis. In this study, we examined the role 
      and mechanism of long noncoding RNA CAMK2D-associated transcript 2 (C2dat2) in 
      regulating CIRI in vivo and in vitro. C2dat2 up-regulation facilitated neuronal 
      autophagy and apoptosis induced by CIRI. Mechanistically, C2dat2 acts as a 
      competing endogenous RNA (ceRNA) to negatively regulate miR-30d-5p expression. 
      More specifically, miR-30d-5p targeted the 3'-untranslated region of DNA 
      damage-inducible transcript 4 (DDIT4) and silenced its target mRNA DDIT4. 
      Additionally, C2dat2 binding with heat shock cognate 70/heat shock protein 90 
      blocked RNA-induced silencing complex assembly to abolish the miR-30d-5p 
      targeting of DDIT4 and inhibited miR-30d-5p to silence its target mRNA DDIT4. 
      Further analysis showed that C2dat2 knockdown conspicuously inhibited the 
      up-regulation of DDIT4 and Beclin-1 levels and LC3B II/I ratio and the 
      down-regulation of P62 and phosphorylated mammalian target of rapamycin 
      (mTOR)/mTOR and phosphorylated-P70S6K/P70S6K ratio in Neuro-2a cells after 
      oxygen-glucose deprivation/reoxygenation. This study first revealed that 
      C2dat2/miR-30d-5p/DDIT4/mTOR forms a novel signaling pathway to facilitate 
      autophagy and apoptosis induced by CIRI, contributing to the better understanding 
      of the mechanisms of CIRI and enriching the ceRNA hypothesis in CIRI.
FAU - Xu, Qian
AU  - Xu Q
AD  - Henan Provincial Engineering Laboratory of Insects Bio-Reactor, Nanyang Normal 
      University, Nanyang 473000, China.
FAU - Guohui, Ma
AU  - Guohui M
AD  - Henan Provincial Engineering Laboratory of Insects Bio-Reactor, Nanyang Normal 
      University, Nanyang 473000, China.
FAU - Li, Dandan
AU  - Li D
AD  - Henan Provincial Engineering Laboratory of Insects Bio-Reactor, Nanyang Normal 
      University, Nanyang 473000, China.
FAU - Bai, Fanghui
AU  - Bai F
AD  - Henan Provincial Nanyang Central Hospital, Nanyang 473000, China.
FAU - Fang, Jintao
AU  - Fang J
AD  - Henan Provincial Engineering Laboratory of Insects Bio-Reactor, Nanyang Normal 
      University, Nanyang 473000, China.
FAU - Zhang, Gui
AU  - Zhang G
AD  - Henan Provincial Engineering Laboratory of Insects Bio-Reactor, Nanyang Normal 
      University, Nanyang 473000, China.
AD  - School of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, 
      Nanyang 473000, China.
FAU - Xing, Yuxin
AU  - Xing Y
AD  - Henan Provincial Engineering Laboratory of Insects Bio-Reactor, Nanyang Normal 
      University, Nanyang 473000, China.
AD  - School of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, 
      Nanyang 473000, China.
FAU - Zhou, Jiawei
AU  - Zhou J
AD  - Henan Provincial Engineering Laboratory of Insects Bio-Reactor, Nanyang Normal 
      University, Nanyang 473000, China.
AD  - School of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, 
      Nanyang 473000, China.
FAU - Guo, Yugang
AU  - Guo Y
AD  - Henan Provincial Engineering Laboratory of Insects Bio-Reactor, Nanyang Normal 
      University, Nanyang 473000, China.
FAU - Kan, Yunchao
AU  - Kan Y
AD  - Henan Provincial Engineering Laboratory of Insects Bio-Reactor, Nanyang Normal 
      University, Nanyang 473000, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210404
PL  - United States
TA  - Aging (Albany NY)
JT  - Aging
JID - 101508617
RN  - 0 (Ddit4 protein, mouse)
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn30d microRNA, mouse)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Apoptosis/genetics
MH  - Autophagy/genetics
MH  - Cell Line, Tumor
MH  - Computational Biology
MH  - Datasets as Topic
MH  - Disease Models, Animal
MH  - Gene Knockdown Techniques
MH  - Gene Regulatory Networks
MH  - Humans
MH  - Ischemic Stroke/*complications/genetics/pathology
MH  - Mice
MH  - MicroRNAs/*metabolism
MH  - Phosphorylation/genetics
MH  - RNA, Long Noncoding/genetics/*metabolism
MH  - Reperfusion Injury/*genetics/pathology
MH  - Signal Transduction/genetics
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Transcription Factors/*genetics
MH  - Up-Regulation
PMC - PMC8109078
OTO - NOTNLM
OT  - apoptosis
OT  - autophagy
OT  - cerebral ischemia-reperfusion injury
OT  - lncRNA
COIS- CONFLICTS OF INTEREST: The authors declare no conflicts of interest.
EDAT- 2021/04/10 06:00
MHDA- 2021/08/03 06:00
PMCR- 2021/04/30
CRDT- 2021/04/09 05:50
PHST- 2020/07/07 00:00 [received]
PHST- 2020/11/20 00:00 [accepted]
PHST- 2021/04/10 06:00 [pubmed]
PHST- 2021/08/03 06:00 [medline]
PHST- 2021/04/09 05:50 [entrez]
PHST- 2021/04/30 00:00 [pmc-release]
AID - 202824 [pii]
AID - 10.18632/aging.202824 [doi]
PST - ppublish
SO  - Aging (Albany NY). 2021 Apr 4;13(8):11315-11335. doi: 10.18632/aging.202824. Epub 
      2021 Apr 4.