Epigenetic regulation and tumor suppressive function of lncRNA EP300-AS1 in nasopharyngeal carcinoma through activation of TFAP2C binding to CST6: implications for diagnosis, prognosis, and therapy.

Abstract

The long non-coding RNA EP300-AS1 (lncRNA EP300-AS1), identified as a potential regulatory factor in various cancers, remains underexplored in nasopharyngeal carcinoma (NPC). This study investigated EP300-AS1's regulatory mechanisms in NPC, particularly its interaction with transcription factor AP-2 Gamma (TFAP2C) and its effect on cystatin E/M (CST6) expression. Employing clinical samples and NPC cell lines, we conducted in vitro and in vivo xenograft experiments to assess the impacts of modulating EP300-AS1 expression. Techniques such as CCK8, migration, scratch, apoptosis assays, cell cycle analysis, immunoblotting, and fluorescence experiments elucidated EP300-AS1's role in NPC. The interaction between EP300-AS1 and TFAP2C in regulating CST6 expression was verified using FISH, ChIP, RNA pull-down, and silver staining assays. Results indicated lower expression levels of EP300-AS1 and CST6 in NPC, with EP300-AS1 suppression inhibiting cell proliferation, migration, and invasion, while promoting apoptosis and maintaining the cell cycle in the G1 phase. EP300-AS1 also modulated epithelial-mesenchymal transition (EMT) marker expression, suggesting a role in metastasis control. Conclusively, EP300-AS1 acts as a potential tumor suppressor in NPC by interacting with TFAP2C and targeting CST6, offering novel biomarkers and therapeutic targets through its influence on methylation and the tumor microenvironment.