H3K18la facilitates nasopharyngeal carcinoma progression through the activation of the IGF2BP1-COX2 signaling pathway.

Nasopharyngeal carcinoma (NPC) is a malignant tumor arising from the nasopharyngeal epithelial mucosa, with its development closely associated with metabolic reprogramming. Lactylation, an epigenetic modification induced by lactate, plays a regulatory role in gene transcription.The precise function and mechanisms of H3K18la in NPC malignancy progression are yet to be clarified.This study demonstrates that the glycolytic pathway is markedly activated in NPC tissues, accompanied by elevated expression of H3K18la, which positively correlates with tumour stage. Subsequent studies showed that lactic acid production, mediated by lactate dehydrogenase A (LDHA), facilitates H3K18la modification. Inhibiting LDHA specifically leads to reduced H3K18la levels, suppressed proliferation of NPC cells, and increased apoptosis.H3K18la upregulates the RNA-binding protein IGF2BP1, while inhibiting LDHA or IGF2BP1 reduces COX2 mRNA stability and expression, influencing NPC cell proliferation and apoptosis resistance. In summary, this study indicates that H3K18la modification is crucial for NPC malignancy through the activation of the IGF2BP1-COX2 signaling pathway. This research elucidates lactylation modification mechanisms in NPC, presenting novel targets for its treatment.