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Silencing of lncRNA XIST impairs angiogenesis and exacerbates cerebral vascular injury after ischemic stroke
- Source :
- Molecular Therapy: Nucleic Acids, Vol 26, Iss, Pp 148-160 (2021), Molecular Therapy. Nucleic Acids
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- The aim of this study was to investigate the function and regulatory mechanism of long non-coding RNA (lncRNA) X-inactive-specific transcript (XIST) in cerebral ischemic stroke (CIS). The impact of lncRNA XIST on CIS was evaluated in acute CIS patients, middle cerebral artery occlusion (MCAO) mice, and oxygen-glucose deprivation and restoration brain endothelial cells. Our results demonstrated that the expression of lncRNA XIST decreased during the early stages of CIS but then increased in the later stages in CIS patients and ischemic models in vivo and in vitro. In addition, the serum levels of lncRNA XIST negatively correlated with severity of neurological impairment of CIS patients. Further studies exhibited that lncRNA XIST regulated the expression of proangiogenic factor-integrin α5 (Itgα5) and anti-inflammation factor-Kruppel-like transcription factor 4 (KLF4) by targeting microRNA-92a (miR-92a). Silencing of lncRNA XIST impaired angiogenesis and exacerbated cerebral vascular injury following CIS, leading to larger infarcts and worse neurological deficits in transient MCAO mice. Mechanistic analysis revealed that lncRNA XIST modulated angiogenesis and alleviated cerebral vascular injury following CIS through mediating the miR-92a/Itgα5 or KLF4 axis, respectively. These data indicate that lncRNA XIST confers protection against CIS, providing a valuable target for future prevention and treatment of CIS.<br />Graphical abstract<br />This study revealed that lncRNA XIST confers protection against cerebral ischemic injury, and the serum levels of lncRNA XIST mirror the severity of cerebral ischemic stroke (CIS), providing a potential biomarker for predicting the prognosis of CIS and also providing a valuable target for future prevention and treatment of CIS.
- Subjects :
- business.industry
Angiogenesis
RNA
RM1-950
blood-brain barrier
Blood–brain barrier
cerebral ischemic stroke
angiogenesis
lncRNA
medicine.anatomical_structure
KLF4
Drug Discovery
Ischemic stroke
miR-92a
Cancer research
Molecular Medicine
Gene silencing
Medicine
Original Article
XIST
Therapeutics. Pharmacology
business
Transcription factor
Subjects
Details
- ISSN :
- 21622531
- Volume :
- 26
- Database :
- OpenAIRE
- Journal :
- Molecular Therapy - Nucleic Acids
- Accession number :
- edsair.doi.dedup.....7662409e3a243d4a238c1971f803ed29