X inactive-specific transcript regulates mitochondrial function and neuronal differentiation of stem cells via IGF2BP2/CPT1A axis in models of spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) often results in irreversible neurological deficits; therefore, effective treatment is urgently needed. Neural stem cells (NSCs) have excellent differentiation potential. However, the role of the long noncoding RNA X inactive-specific transcript (XIST) in NSCs and SCI remains unclear. AIM: To explore the role of XIST in enhancing NSC function and its therapeutic potential in SCI. METHODS: We used in vitro and in vivo models to examine the effects of XIST on NSCs. XIST was overexpressed in NSCs, and its impact on mitochondrial function, neuronal differentiation, and the insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2)/carnitine palmitoyl transferase 1A (CPT1A) pathway was assessed using a series of biochemical assays, quantitative PCR, and Seahorse XF24 analysis. A mouse model of SCI was used to evaluate the therapeutic effects of XIST in vivo. RESULTS: Overexpression of XIST in NSCs significantly increased mitochondrial membrane potential, ATP production, and oxygen consumption rate. XIST also promoted NSC proliferation and neuronal differentiation while inhibiting astrocytic differentiation. Mechanistically, XIST regulated CPT1A expression post-transcriptionally by interacting with IGF2BP2. In vivo XIST-treated mice exhibited improved motor scores and reduced proinflammatory cytokine expression following SCI. CONCLUSION: These findings suggested that XIST modulated mitochondrial function and neural differentiation in NSCs through the IGF2BP2/CPT1A pathway. While preliminary in vivo results are encouraging, further studies are needed to determine the long-term therapeutic relevance and underlying mechanisms of XIST in SCI recovery.