TY  - EJOU
AU  - Liu, Siliang 
AU  - Tang, Hong 
AU  - Xia, Ying 
AU  - Yu, Zhengtao 
AU  - Gao, Ning 

TI  - C-Myc Reduces Oxygen-Glucose Deprivation/Reperfusion-Induced Neuronal Pyroptosis through the SRSF1/NLRP1 Axis
T2  - BIOCELL

PY  - 2025
VL  - 49
IS  - 7
SN  - 1667-5746

AB  -  <b>Objectives:</b> NOD-like receptor family pyrin domain-containing (NLRP) 1-mediated pyroptosis plays a key role in the pathogenesis of cerebral ischemia-reperfusion injury (CIRI). C-Myc is reported to play a major role in CIRI. However, the mechanism remains unclear. This study aimed to investigate whether c-Myc affects CIRI by regulating Serine/Arginine-rich Splicing Factor 1 (SRSF1)/NLRP1-mediated pyroptosis. <b>Methods:</b> Oxygen-glucose deprivation/reperfusion (OGD/R) induced neuroblastoma cells for the establishment of an <i>in vitro</i> CIRI model. The levels of c-Myc and SRSF1, cell viability, the expression of pyroptosis-related factors, and the interaction between SRSF1 and NLRP1 were evaluated. <b>Results:</b> The expression of c-Myc and SRSF1 was decreased in OGD/R-induced neuroblastoma cells. c-Myc overexpression increased c-Myc and SRSF1 expression and cell viability in OGD/R-induced neuroblastoma cells while inhibiting NLRP1, Caspase1, apoptosis-associated speck-like protein containing a CARD (ASC), interleukin-1beta (IL-1β), IL-18, and lactate dehydrogenase levels and pyroptosis. C-Myc was positively correlated with SRSF1. SRSF1 low expression reversed the effects of c-Myc on the above indicators in OGD/R-induced neuroblastoma cells. Mechanically, SRSF1 interacted with NLRP1. SRSF1 was negatively correlated with NLRP1. The NLRP1 activator muramyl dipeptide (MDP) reversed the SRSF1 effect on OGD/R-induced neuroblastoma cells. <b>Conclusion:</b> Our results indicated that c-Myc reduced OGD/R-induced neuroblastoma cell pyroptosis by inhibiting NLRP1 activation by positive feedback SRSF1 signal. Our findings suggested that the c-Myc/SRSF1 axis might be a new strategy for treating CIRI in the clinic.
KW  - Cerebral ischemia-reperfusion injury; pyroptosis; c-Myc; SRSF1; NLRP1

DO  - 10.32604/biocell.2025.064396