GAS5 silencing protects against hypoxia/ischemia-induced neonatal brain injury
Hypoxic/ischemic 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, w...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2018-02, Vol.497 (1), p.285-291 |
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| creator | Zhao, Rui-bin Zhu, Li-hua Shu, Jia-Ping Qiao, Li-Xing Xia, Zheng-Kun |
| description | Hypoxic/ischemic 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.
•GAS5 expression is increased after neonatal hypoxic/ischemic brain injury.•GAS5 knockdown protects hippocampal cells against hypoxic/ischemic stress.•GAS5 regulates hippocampal neuron function by sponging miR-23a.•GAS5 knockdown alleviates hypoxic/ischemic brain injury in vivo. |
| doi_str_mv | 10.1016/j.bbrc.2018.02.070 |
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•GAS5 expression is increased after neonatal hypoxic/ischemic brain injury.•GAS5 knockdown protects hippocampal cells against hypoxic/ischemic stress.•GAS5 regulates hippocampal neuron function by sponging miR-23a.•GAS5 knockdown alleviates hypoxic/ischemic brain injury in vivo.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2018.02.070</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; ANOXIA ; BRAIN ; Brain damage ; INFANTS ; INJURIES ; ISCHEMIA ; Long noncoding RNA ; microRNA sponge ; NERVE CELLS ; RNA ; Therapeutic approach</subject><ispartof>Biochemical and biophysical research communications, 2018-02, Vol.497 (1), p.285-291</ispartof><rights>2018 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c427t-823f88ab86a028b8877448a3d9046a6ac14d040a44f0fcaaa4ab687b2305375b3</citedby><cites>FETCH-LOGICAL-c427t-823f88ab86a028b8877448a3d9046a6ac14d040a44f0fcaaa4ab687b2305375b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbrc.2018.02.070$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttps://www.osti.gov/biblio/23137340$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhao, Rui-bin</creatorcontrib><creatorcontrib>Zhu, Li-hua</creatorcontrib><creatorcontrib>Shu, Jia-Ping</creatorcontrib><creatorcontrib>Qiao, Li-Xing</creatorcontrib><creatorcontrib>Xia, Zheng-Kun</creatorcontrib><title>GAS5 silencing protects against hypoxia/ischemia-induced neonatal brain injury</title><title>Biochemical and biophysical research communications</title><description>Hypoxic/ischemic 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.
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•GAS5 expression is increased after neonatal hypoxic/ischemic brain injury.•GAS5 knockdown protects hippocampal cells against hypoxic/ischemic stress.•GAS5 regulates hippocampal neuron function by sponging miR-23a.•GAS5 knockdown alleviates hypoxic/ischemic brain injury in vivo.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><doi>10.1016/j.bbrc.2018.02.070</doi><tpages>7</tpages></addata></record> |
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| subjects | 60 APPLIED LIFE SCIENCES ANOXIA BRAIN Brain damage INFANTS INJURIES ISCHEMIA Long noncoding RNA microRNA sponge NERVE CELLS RNA Therapeutic approach |
| title | GAS5 silencing protects against hypoxia/ischemia-induced neonatal brain injury |
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