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Onco Targets Ther. 2018 Nov 1;11:7613-7624. doi: 10.2147/OTT.S179866. eCollection 2018.

SIRT6 overexpression induces apoptosis of nasopharyngeal carcinoma by inhibiting NF-κB signaling.

Author information

1
Department of Otolaryngology, Head and Neck Surgery, the Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, People's Republic of China, lissdoctor@csu.edu.cn.
2
Department of Otolaryngology, Head and Neck Surgery, the Affiliated Hospital of Guilin Medical College, the Institute of Otolaryngology of Guilin Medical College, Guilin, 541001 Guangxi, People's Republic of China, glmclp@126.com.

Abstract

Background:

Previous reports show that SIRT6 serves as a critical modulator of the development of multiple malignancies as well as other disorders. However, its role in nasopharyngeal carcinoma (NPC) is unknown. Thus, we elucidated the effects of SIRT6 on the survival of NPC cells, and modulation of cell death.

Methods:

We found that expression of SIRT6 is downregulated in ten human NPC specimens as well as in the human NPC cell lines, 5-8 F and CNE1, as compared with that in healthy tissues and normal nasopharyngeal NP69 cells. The MTT assay and colony formation assay revealed that upregulation of SIRT6 impaired the proliferation, as well as the survival of 5-8 F and CNE1 cells. The TUNEL assay, annexin V-FITC/propidium iodide, and flow cytometry were performed to detect apoptosis. The results revealed that the expression of SIRT6 resulted in increased apoptosis.

Results:

Western blotting results showed that SIRT6 overexpression decreased anti-apoptotic Bcl-2 levels, whereas it promoted an increase in pro-apoptotic Bax and cleaved caspase-3 levels. Moreover, NF-κB levels were markedly reduced in cells expressing SIRT6, whereas they were increased in cells transfected with shRNA-SIRT6. Recovery of NF-κB expression was found to counter the suppressive influence of SIRT6 on NPC cell survival, whereas, NF-κB knockdown increased apoptosis of NPC cells.

Conclusion:

Thus, the findings of our study offer insight into the biological and molecular mechanisms underlying the development of NPC and may lead to the development of new and innovative strategies for the treatment of NPC.

KEYWORDS:

NF-κB; SIRT6; apoptosis; nasopharyngeal carcinoma

Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

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