Cancer Management and Research (Oct 2020)

CYLD Promotes Apoptosis of Nasopharyngeal Carcinoma Cells by Regulating NDRG1

  • Lin Y,
  • Wang L,
  • Luo W,
  • Zhou X,
  • Chen Y,
  • Yang K,
  • Liao J,
  • Wu D,
  • Cai L

Journal volume & issue
Vol. Volume 12
pp. 10639 – 10649

Abstract

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Yanling Lin,1,* Lingzhi Wang,2,* Wenxiao Luo,1,* Xiaohan Zhou,1 Yuting Chen,1 Kaifan Yang,3 Jinrong Liao,4 Dehua Wu,1 Longmei Cai1 1Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2First Clinical Medical College, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 3Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 4Second Clinical Medical College, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dehua Wu; Longmei CaiDepartment of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People’s Republic of ChinaTel +86 186 0206 2748; +86 134 5020 5073Email [email protected]; [email protected]: 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 (CYLD); 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 CYLD 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 CYLD in vivo.Results: We found that CYLD levels were significantly decreased in both NPC tissues and cell lines, and that CYLD 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 NDRG1 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.Keywords: NPC, CYLD, proliferation, apoptosis, NDRG1

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