Knockdown of SUCLG2 inhibits glioblastoma proliferation and promotes apoptosis through LMNA acetylation and the mediation of H4K16la lactylation.

Glioblastoma (GBM) is the most aggressive primary tumour in the central nervous system, and dynamic clonal evolution and interactions within the microenvironment cause its significant spatiotemporal heterogeneity. These interactions primarily manifest as metabolic reprogramming, mitochondrial dynamic imbalance, and epigenetic remodelling. SUCLG2 has been implicated in the progression of GBM; however, the underlying mechanism is unclear. This study aimed to investigate the role of SUCLG2 in the proliferation and apoptosis of GBM cells. SUCLG2 was found to interact with LMNA, leading to acetylation modification of its amino acid residue K470 and affecting limited oxidative phosphorylation levels and mitochondrial damage. SUCLG2 interacted with DLAT, reducing the binding of lactate-regulated protein H4K16la to promoter regions and cis-regulatory elements. This suppressed the expression of BEST1, GRAMD4, and MBD6, affecting the proliferation and apoptosis of GBM cells. These findings reveal a new SUCLG2-mediated mechanism in lactate metabolism and mitochondrial apoptosis in GBM and offer novel therapeutic and preventive targets for GBM.