Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 497, Issue 1, Pages 285-291Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2018.02.070
Keywords
Long noncoding RNA; Brain damage; microRNA sponge; Therapeutic approach
Categories
Funding
- Clinical Advanced Techniques, Primary Research & Development Plan of Jiangsu Province [BE2017719]
- Pediatric Medical Innovation Team of Jiangsu Province [CXTDA2017022]
- National youth fund [81601355]
- Jiangsu province [1701162C]
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Hypoxiclischemic brain damage (HIBD) leads to high neonatal mortality and severe neurologic morbidity. However, the molecular mechanism of HIBD in the neonatal infant is still elusive. Long non coding RNAs are shown as important regulators of brain development and many neurological diseases. Here, we determined the role of long noncoding RNA-GAS5 in HIBD. GAS5 expression was significantly up-regulated in hypoxic/ischemic-injured neonatal brain and hippocampal neurons. GAS5 silencing protected against hypoxic/ischemic-induced brain injury in vivo and primary hippocampal neuron injury in vitro. Mechanistically, GAS5 regulated hippocampal neuron function by sponging miR-23a. Intracerebroventricular injection of GAS5 shRNA significantly decreased brain GAS5 expression, reduced brain infarct size, and improved neurological function recovery. Collectively, this study suggests a promising therapeutic approach of GAS5 inhibition in the treatment of neonatal HIBD. (C) 2018 Elsevier Inc. All rights reserved.
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