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

• Published in: Molecular medicine (Cambridge, Mass.) Vol. 27; no. 1; p. 107
• Main Authors: Chen, Zhongjun, Fan, Tieping, Zhao, Xusheng, Zhang, Zhichen
• Format: Journal Article
• Language: English
• Published: England BioMed Central 14-09-2021; BMC
• Subjects: Animals; Biomarkers; Cell Line; Disease Susceptibility; Gene Expression Regulation; Genes, Reporter; Humans; Immunohistochemistry; Ischemic stroke; Ischemic Stroke - etiology; Ischemic Stroke - metabolism; Ischemic Stroke - pathology; Long non-coding RNA plasmacytoma variant translocation 1; Male; MicroRNA-24-3p; MicroRNAs - genetics; Oxidative Stress; Rats; RNA Interference; RNA, Long Noncoding - genetics; Sex determining region Y-box 2; Signal transducer and activator of transcription 3; Signal Transduction; SOXB1 Transcription Factors - genetics; SOXB1 Transcription Factors - metabolism; STAT3 Transcription Factor - metabolism; Long non-coding RNA plasmacytoma variant translocation 1; Oxidative stress; MicroRNA-24-3p; Ischemic stroke; Sex determining region Y-box 2; Signal transducer and activator of transcription 3
• ISSN: 1076-1551; 1528-3658
• DOI: 10.1186/s10020-021-00346-8

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.
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.
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.
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.