CYLD Promotes Apoptosis of Nasopharyngeal Carcinoma Cells by Regulating NDRG1.

PURPOSE

Nasopharyngeal carcinoma (NPC) is among the most common malignancies derived from the epithelium of the nasopharynx. To date, the regulatory networks involved in NPC have not been fully identified. Previous studies revealed multiple loss-of-function mutations in NPC and specifically in cylindromatosis lysine 63 deubiquitinase (); however, the exact role of CYLD in NPC progression and its potential mechanism remains unclear.

METHODS

We performed immunohistochemical (IHC) staining and real-time quantitative polymerase chain reaction (qPCR) to measure expression in NPC tissues, and Western blot was conducted to determine CYLD levels in NPC cell lines. Cell proliferation was detected by CCK8 assay and colony formation analysis, and apoptosis was determined by Annexin V/propidium iodide staining. Potential targets of CYLD were verified by co-immunoprecipitation and mass spectrometry. Xenograft assay was conducted to confirm the role of in vivo.

RESULTS

We found that CYLD levels were significantly decreased in both NPC tissues and cell lines, and that overexpression inhibited NPC cell proliferation and promoted apoptosis. Additionally, we revealed that CYLD bound and upregulated N-Myc downstream regulated 1 (NDRG1), and that silencing abolished the tumor-suppressor effect of CYLD on NPC cells. Furthermore, CYLD suppressed tumor growth in xenograft mice models.

CONCLUSION

These results suggest CYLD as a tumor suppressor, potential biomarker for diagnosing NPC, and therapeutic target.