Mechanism of SOX10 in ferroptosis of hippocampal neurons after intracerebral hemorrhage via the miR-29a-3p/ACSL4 axis.

ABSTRACT

Intracerebral hemorrhage (ICH) is classified as a lethal neurological injury associated with cerebrovascular disorders. Ferroptosis is a unique form of cell death and participates in ICH pathogenesis. Herein, the role of SRY-box transcription factor 10 (SOX10) in ferroptosis of hippocampal neurons after ICH was investigated. The in vitro ICH models were established by treating immortalized mouse hippocampal cell line HT-22 with Hemin. Quantitative real-time polymerase chain reaction and Western blotting revealed that the transcription factor SOX10 and microRNA (miR)-29a-3p were decreased whereas acyl-CoA synthetase long-chain family member 4 (ACSL4) was increased in the ICH cell models. Subsequently, the assays of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, the commercial kits, and fluorescent labeling revealed that SOX10 overexpression improved cell viability, decreased the amount of reactive oxygen species (ROS) and Fe2+, and increased the amount of glutathione (GSH) and glutathione peroxidase 4 (GPX4) in ICH models. Thereafter, chromatin immunoprecipitation and dual-luciferase assays showed that SOX10 binding to the miR-29a-3p promoter region increased miR-29a-3p expression, and miR-29a-3p targeted and limited ACSL4 transcription. Rescue experiments showed that miR-29a-3p downregulation or ACSL4 overexpression expedited ferroptosis of Hemin-treated HT-22 cells. Taken together, SOX10 contributed to ferroptosis of hippocampal neurons after ICH via increasing miR-29a-3p to limit ACSL4 transcription.NEW & NOTEWORTHY SOX10 promotes the expression of Mir-29a-3p by binding to the promoter region of Mir-29a-3p, thereby targeting the expression of ACSL4 and inhibiting the iron death of hippocampal neuronal cells in mice with ICH.