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Blocking lncRNA
- Source :
- Aging (Albany NY)
- Publication Year :
- 2019
-
Abstract
- Elevated expression of lncRNA H19 (H19) in the setting of hypoxia has been implicated as a promising therapeutic target for various cancers. However, little is known about the impact and underlying mechanism of H19 in ischemic brain stroke. This study found that H19 levels were elevated in the serum of stroke patients, as well as in the ischemic penumbra of rats with middle cerebral artery occlusion/reperfusion (MCAO/R) injury and neuronal cells with oxygen glucose deprivation (OGD). Further, knockdown of H19 with siRNA alleviated cell apoptosis in OGD neuronal cells, and inhibition of H19 in MCAO/R rats significantly decreased neurological deficit, brain infarct volume and neuronal apoptosis. Lastly, with gain and loss of function studies, dual luciferase reported assay, RNA immunoprecipitation (RIP) and pull-down experiments, we demonstrated the dual competitive interaction of miR-19a with H19 and the 3’-UTR of Id2 mRNA, resulting in the identification of the H19-miR-19a-Id2 axis. With biological studies, we also revealed that H19-miR-19a-Id2 axis modulated hypoxia induced neuronal apoptosis. This study demonstrates that the identified H19-miR-19a-Id2 axis plays a critical role in hypoxia induced neuronal apoptosis, and blocking this axis may serve as a novel therapeutic strategy for ischemic brain injury.
- Subjects :
- Male
Apoptosis
ischemia
Id2
Cell Line, Tumor
Animals
Humans
RNA, Small Interfering
Aged
Inhibitor of Differentiation Protein 2
Neurons
hypoxia
miR-19a
Middle Aged
female genital diseases and pregnancy complications
Rats
Stroke
Disease Models, Animal
MicroRNAs
lncRNA H19
nervous system
embryonic structures
Hypoxia-Ischemia, Brain
Female
RNA, Long Noncoding
Research Paper
Subjects
Details
- ISSN :
- 19454589
- Volume :
- 11
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Aging
- Accession number :
- edsair.pmid..........8dbce28d62534c95719379d8cca0ff84