Abstract
ObjectivesStudies 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.MethodsRat 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.ResultsSOX2, 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.ConclusionThis 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.
Highlights
Ischemic stroke (IS) is generally considered as a leading cause of death and disability around the world (Liu et al 2015)
Sex determining region Y-box 2 (SOX2), plasmacytoma variant translocation 1 (PVT1) and signal transducer and activator of transcription 3 (STAT3) are highly expressed while miR‐24‐3p is poorly expressed in brain tissues in middle cerebral artery occlusion (MCAO) rats RT-qPCR, Western blot and immunohistochemistry were used to detect SOX2, PVT1, miR-24-3p, and STAT3 expression in cerebral cortex in each group
The results demonstrated that relative to the sham group, SOX2, Inhibited SOX2 or PVT1 upregulates miR‐24‐3p expression and downregulate STAT3 expression in MCAO rats It was indicated by RT-qPCR and Western blot analysis (Fig. 2A–C) that the shRNA targeting SOX2 lentiviral vector (sh-SOX2) group showed reduced PVT1 and STAT3 expression and increased miR-24-3p expression versus the sh-Negative control (NC) group; by contrast to the sh-PVT1 NC lentiviral vector (sh-CTR) group, the shRNA targeting PVT1 lentiviral vector (sh-PVT1) group presented decreased STAT3 expression and elevated miR-24-3p expression; with respect to the Lenti-NC group, the Lenti-PVT1 group exhibited increased STAT3 expression and decreased miR-24-3p expression
Summary
Ischemic stroke (IS) is generally considered as a leading cause of death and disability around the world (Liu et al 2015). Sex determining region Y-box 2 (SOX2) is a transcription factor that regulates self-renewal and differentiation of embryonic stem cells (Li et al 2012). It is recorded that SOX2 expression is elevated after hypoxia in cerebral ischemia (Han et al 2017). SOX2 is found to be highly expressed in the hippocampus after traumatic brain injury (Gu et al 2016). MicroRNAs (miRs) function in the processes of neurodegenerative diseases and certain neurological diseases including IS (Eyileten et al 2018). MiR-24-3p is correlated with angiogenic factors that have been associated with recurrent ischemic events in intracranial
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
