PRELID2 promotes the progression of nasopharyngeal carcinoma by positively regulating the TXNDC12-GSH-GPX4 axis and inhibiting ferroptosis.

BACKGROUND

Nasopharyngeal carcinoma (NPC) treatment is challenged by advanced metastasis, high recurrence rates, and resistance to both radiotherapy and chemotherapy. PRELI domain-containing protein 2 (PRELID2) is overexpressed in cancers and linked to poor prognosis, but its role in NPC remains unclear.

METHODS

We utilized public datasets to analyze the expression characteristics and clinical prognostic significance of PRELID2 in NPC. The expression of PRELID2 in NPC cell lines was validated through Western blotting and quantitative reverse transcription PCR (qRT-PCR). The effects of PRELID2 on NPC cell proliferation, migration, and invasion were assessed using in vitro functional assays, such as CCK-8, colony formation, Transwell, wound healing assays, and an in vivo subcutaneous xenograft tumor model in nude mice. Downstream mechanisms were investigated through RNA-seq and rescue experiments.

RESULTS

Both mRNA and protein levels of PRELID2 were elevated in NPC cells, and associated with poorer survival. In vitro experiments demonstrated that overexpression of PRELID2 significantly enhanced NPC cell proliferation, migration, and invasion. In vivo experiments confirmed that silencing PRELID2 markedly suppressed the growth of subcutaneous xenograft tumors in nude mice. RNA-seq and functional rescue validation revealed that PRELID2 positively regulates the expression of thioredoxin domain-containing protein 12 (TXNDC12), increasing intracellular GSH levels. The accumulation of GSH enhances GPX4 activity, effectively inhibiting ferroptosis in NPC cells and ultimately promoting tumor progression.

CONCLUSION

PRELID2 promotes NPC by upregulating TXNDC12 to sustain GSH levels, thereby enhancing GPX4 activity, inhibiting ferroptosis, and driving tumor growth. Suggest PRELID2 as a potential prognostic biomarker and therapeutic target for NPC.