Open Access

ARTICLE

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

Siliang Liu^1,#, Hong Tang^2,#, Ying Xia¹, Zhengtao Yu¹, Ning Gao^1,*

1 Department of Neurosurgery, Affiliated Haikou Hospital, Xiangya Medical College of Central South University, Haikou, 570208, China
2 Department of Neurosurgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, 233099, China

* Corresponding Author: Ning Gao. Email:
#Siliang Liu and Hong Tang are co-first authors, contributed equally to this study

BIOCELL 2025, 49(7), 1245-1264. https://doi.org/10.32604/biocell.2025.064396

Received 14 February 2025; Accepted 15 May 2025; Issue published 25 July 2025

Abstract

Objectives: 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. Methods: Oxygen-glucose deprivation/reperfusion (OGD/R) induced neuroblastoma cells for the establishment of an in vitro 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. Results: 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. Conclusion: 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.

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