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

Abstract

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.

Identification of hypoxia- and immune-related biomarkers in patients with ischemic stroke

“…Serum miR-32-3p, miR-148b-3p, miR-151b, let-7e-5p, miR-23b-3p, miR-29b-3p, miR-186-5p, miR-30a-5p, miR-124-3p, miR-128-3p, miR-192-5p, miR-222, miR-17-5p, and miR-221-3p may serve as potential diagnostic biomarkers for IS [ [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] ]. Depleting sex-determining region Y-box 2 (SOX2) enhanced IS by the PVT1/miR-24-3p/STAT3 axis [ 63 ]. miR-335-5p, let-7b-5p, miR-34a-5p, and miR-3622b-5p have been reported as therapeutic targets or diagnostic biomarkers regarding IS treatment [ [64] , [65] , [66] , [67] ].…”

Crosstalk between oxidative stress and neutrophil response in early ischemic stroke: a comprehensive transcriptome analysis

“…STAT3, a relatively conserved member of the STATs family, transduces signal pathways for transcriptional regulation of cellular homeostasis, proliferation, inflammation, etc ( 14 ). Previous experiments have observed that STAT3 expression levels were increased in the rat brain regions ipsilateral to middle cerebral artery occlusion (MCAO) relative to the sham group ( 15 , 16 ). Moreover, Adly et al.…”

Pathophysiology of Ischemic Stroke: Noncoding RNA Role in Oxidative Stress

“…In lncRNA PVT1-inhibited MCAO rats, oxidative stress and neuron apoptosis were limited, and neurological impairments improved. In MCAO rats, the lncRNA PVT1 was activated by the sex-determining region Y-box 2 (SOX), sponged miR-24-3p, and regulated STAT3 expression [ 104 ].…”