Abstract
Epigenetic regulation plays a crucial role in the development of nasopharyngeal carcinoma (NPC). However, the epigenetic mechanisms underlying NPC recurrence and metastasis remain poorly understood. This study aimed to investigate and identify a novel molecular target with prognostic relevance in NPC. The methylation status of zinc finger protein 844 (ZNF844) was assessed in NPC tissues and cell lines using bisulfite pyrosequencing. ZNF844 expression levels in NPC cell lines and clinical specimens were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. Stable NPC cell lines with ZNF844 overexpression or knockdown were established to evaluate its biological functions both in vitro and in vivo. RNA sequencing was performed to identify downstream targets of ZNF844, followed by validation using qRT-PCR and Western blotting. We found that ZNF844 expression was significantly downregulated in NPC tissues and cell lines, correlating with hypermethylation of its promoter region. Treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (DAC) restored ZNF844 mRNA expression. ZNF844 overexpression suppressed NPC cell invasion and metastasis, whereas its silencing had the opposite effect. In xenograft models, ZNF844 overexpression reduced metastatic burden. ZNF844 inhibited the PI3K-AKT signaling pathway, thereby suppressing NPC cell invasiveness. Clinically, high ZNF844 expression was associated with improved overall survival and distant metastasis-free survival. ZNF844 inhibits the invasive and metastatic capabilities of nasopharyngeal carcinoma by modulating the PI3K-AKT signaling pathway. These inhibitory effects can be partially or completely reversed by treatment with SC79. It may serve as a promising therapeutic target and prognostic biomarker for NPC.