Open Access

FOXO3a‑SIRT6 axis suppresses aerobic glycolysis in melanoma

  • Authors:
    • Zhen Dong
    • Jie Yang
    • Lin Li
    • Li Tan
    • Pengfei Shi
    • Jiayi Zhang
    • Xi Zhong
    • Lingjun Ge
    • Zonghui Wu
    • Hongjuan Cui
  • View Affiliations

  • Published online on: January 17, 2020     https://doi.org/10.3892/ijo.2020.4964
  • Pages: 728-742
  • Copyright: © Dong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Melanoma, the most aggressive human skin tumor, has a very short survival time, and there are currently no effective treatments. Alterations in cell metabolism, such as enhanced aerobic glycolysis, have been identified as hallmarks of cancer cells. In the present study, bioinformatics studies using online databases revealed that FOXO3a expression was lower in melanoma tissues compared with normal tissues and nevus. Additionally, Kaplan‑Meier analysis showed that high expression of FOXO3a predicted an improved prognosis for patients with melanoma. Furthermore, Pearson correlation analysis indicated that the expression of FOXO3a was positively correlated with SIRT6 expression and negatively correlated with the expression levels of a number of glycolysis‑associated genes. Chromatin immunoprecipitation and luciferase assays showed that FOXO3a was enriched in the SIRT6 promoter region and promoted its transcription. Then, SIRT6 was overexpressed in FOXO3a‑knockdown MV3 cells and downregulated in FOXO3a‑overexpressing MV3 cells by using lentivirus‑mediated stable infection. The results showed that SIRT6 knockdown or overexpression rescued the effects of FOXO3a overexpression or knockdown, respectively, on glycolysis, as determined by glucose uptake, glucose consumption and lactate production assays, the expression of glycolytic genes and glucose stress flux tests. SIRT6 overexpression also suppressed FOXO3a knockdown‑induced tumor growth in a mouse model. The present findings indicated that the FOXO3a‑SIRT6 regulatory axis inhibited glucose metabolism and tumor cell proliferation in melanoma, and provided novel insight into potential therapeutic strategies to treat this disease.
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March 2020
Volume 56 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Dong, Z., Yang, J., Li, L., Tan, L., Shi, P., Zhang, J. ... Cui, H. (2020). FOXO3a‑SIRT6 axis suppresses aerobic glycolysis in melanoma. International Journal of Oncology, 56, 728-742. https://doi.org/10.3892/ijo.2020.4964
MLA
Dong, Z., Yang, J., Li, L., Tan, L., Shi, P., Zhang, J., Zhong, X., Ge, L., Wu, Z., Cui, H."FOXO3a‑SIRT6 axis suppresses aerobic glycolysis in melanoma". International Journal of Oncology 56.3 (2020): 728-742.
Chicago
Dong, Z., Yang, J., Li, L., Tan, L., Shi, P., Zhang, J., Zhong, X., Ge, L., Wu, Z., Cui, H."FOXO3a‑SIRT6 axis suppresses aerobic glycolysis in melanoma". International Journal of Oncology 56, no. 3 (2020): 728-742. https://doi.org/10.3892/ijo.2020.4964