Depleting SOX2 improves ischemic stroke via lncRNA PVT1/microRNA-24-3p/STAT3 axis

Autor: Tieping Fan, Zhongjun Chen, Xusheng Zhao, Zhichen Zhang
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
STAT3 Transcription Factor
medicine.medical_specialty
RM1-950
QD415-436
medicine.disease_cause
Biochemistry
Sex determining region Y-box 2
Cell Line
Genes
Reporter
Internal medicine
microRNA
Long non-coding RNA plasmacytoma variant translocation 1
Genetics
medicine
Animals
Humans
STAT3
Molecular Biology
Transcription factor
Genetics (clinical)
Ischemic stroke
Signal transducer and activator of transcription 3
MicroRNA-24-3p
biology
business.industry
SOXB1 Transcription Factors
Immunohistochemistry
Rats
PVT1
MicroRNAs
Endocrinology
medicine.anatomical_structure
Gene Expression Regulation
Apoptosis
Cerebral cortex
Oxidative stress
biology.protein
STAT protein
Molecular Medicine
RNA Interference
RNA
Long Noncoding
Disease Susceptibility
Therapeutics. Pharmacology
business
Biomarkers
Research Article
Signal Transduction
Zdroj: Molecular Medicine, Vol 27, Iss 1, Pp 1-12 (2021)
Molecular Medicine
ISSN: 1528-3658
1076-1551
Popis: Objectives Studies have widely explored in the filed of ischemic stroke (IS) with their focus on transcription factors. However, few studies have pivoted on sex determining region Y-box 2 (SOX2) in IS. Thus, this study is launched to figure out the mechanisms of SOX2 in IS. Methods Rat middle cerebral artery occlusion (MCAO) was established as a stroke model. MCAO rats were injected with depleted SOX2 or long non-coding RNA plasmacytoma variant translocation 1 (PVT1) to explore their roles in neurological deficits, cerebral water content, neuron survival, apoptosis and oxidative stress. The relationship among SOX2, PVT1, microRNA (miR)-24-3p and signal transducer and activator of transcription 3 (STAT3) was verified by a series of experiments. Results SOX2, PVT1 and STAT3 were highly expressed while miR-24-3p was poorly expressed in cerebral cortex tissues of MCAO rats. Depleted SOX2 or PVT1 alleviated brain injury in MCAO rats as reflected by neuronal apoptosis and oxidative stress restriction, brain water content reduction, and neurological deficit and neuron survival improvements. Overexpression of PVT1 functioned oppositely. Restored miR-24-3p abolished PVT1 overexpression-induced brain injury in MCAO rats. SOX2 directly promoted PVT1 expression and further increased STAT3 by sponging miR-24-3p. Conclusion This study presents that depleting SOX2 improves IS via PVT1/miR-24-3p/STAT3 axis which may broaden our knowledge about the mechanisms of SOX2/PVT1/miR-24-3p/STAT3 axis and provide a reference of therapy for IS.
Databáze: OpenAIRE
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