Actl6a regulates autophagy via Sox2-dependent Atg5 and Atg7 expression to inhibit apoptosis in spinal cord injury

作者：Jian Hao, Yubiao Yang, Li Xie, Zhenhan Li, Boyuan Ma, Bitao Wang, Jinyu Chen, Zhi Zeng, Xianhu Zhou · 发表于：Journal of Advanced Research · 年份：2025 · DOI：10.1016/j.jare.2025.01.038 · 被引用次数：7 · 研究领域：RNA modifications and cancer、Protein Tyrosine Phosphatases、interferon and immune responses

Fto-Actl6a-Sox2 Pathway in SCI Recovery Fto regulates m6A methylation of Actl6a mRNA, influencing its stability and expression. Actl6a and Sox2 co-regulate the autophagy genes Atg5 and Atg7, promoting autophagy, reducing apoptosis, and enhancing neural cell survival post-SCI. • Actl6a enhances autophagy and inhibits neuronal apoptosis, promoting spinal cord injury (SCI) repair. • Actl6a directly interacts with Sox2 to upregulate Atg5 and Atg7, exerting protective effects on neurons during SCI. • Fto-mediated m6A methylation regulates Actl6a mRNA stability, emphasizing its role in injury response. Spinal cord injury (SCI) is a severe central nervous system disorder with limited treatment options. While autophagy plays a protective role in neural repair, its regulatory mechanisms in SCI remain unclear. Actin-like protein 6A (Actl6a) influences cell fate and neural development, yet its specific role in SCI repair is not well understood. This study investigates Actl6a’s function in regulating autophagy and apoptosis via the transcription factor Sox2 in SCI. This study aims to determine if Actl6a promotes neural survival post-SCI by regulating autophagy-related genes Atg5 and Atg7 through Sox2. It also examines how the demethylase Fto modulates Actl6a mRNA stability via m6A methylation. In vitro experiments were conducted using primary neurons and HT-22 hippocampal cells exposed to hydrogen peroxide (H 2 O 2 )-induced oxidative stress. Actl6a expression was manipulated by knockdow...