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SIRT7 promotes thyroid tumorigenesis through phosphorylation and activation of Akt and p70S6K1 via DBC1/SIRT1 axis

Oncogene volume 38, pages 345–359 (2019)Cite this article

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Abstract

SIRT7 is an NAD+-dependent histone/non-histone deacetylase, which is highly expressed in different types of cancer including thyroid cancer; however, its biological function in thyroid cancer is still undiscovered. In this study, we found that SIRT7 expression was elevated in papillary thyroid cancers (PTCs), and demonstrated that SIRT7 knockdown dramatically inhibited the proliferation, colony formation, migration and invasion of thyroid cancer cells, and induced thyroid cancer cell cycle arrest and apoptosis. Conversely, SIRT7 re-expression markedly enhanced thyroid cancer cell growth, invasiveness and tumorigenic potential in nude mice. Further studies revealed that SIRT7 exerted an oncogenic function in thyroid tumorigenesis by phosphorylation of Akt and p70S6K1. Mechanistically, SIRT7 binds to the promoter of deleted in breast cancer-1 (DBC1), an endogenous inhibitor of SIRT1, and represses its transcription via deacetylation of H3K18Ac. This results in enhanced interactions between SIRT1 and Akt or p70S6K1, thereby promoting deacetylation and subsequent phosphorylation of Akt and p70S6K1 through a SIRT1-dependent manner. Altogether, our results show that DBC1 is a downstream target of SIRT7, and first uncover that SIRT7 promotes thyroid tumorigenesis through phosphorylation and activation of Akt and p70S6K1 via the modulation of DBC1/SIRT1 axis.

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Acknowledgements

We would like to thank Drs. Haixia Guan (The First Affiliated Hospital of China Medical University, Shenyang, China) and Lei Ye (Ruijin Hospital, Shanghai, China) for kindly providing human thyroid cancer cell lines. This work was supported by the National Natural Science Foundation of China (no. 81372217, 81572627 and 81672645), and the China International Medical Foundation (no. 2016-N-07-12).

Author contributions

PH and MJ conceived and designed the experiments. HL, ZT, YQ and QY conducted the experiments. HL, MJ and PH analyzed the data. HG, BS and PH contributed reagents and materials. HL and PH wrote the paper.

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Authors and Affiliations

  1. Department of Endocrinology, The First Affiliated Hospital of Xi’an Jiaotong University, 710061, Xi’an, P. R. China

    Heng Li, Yiping Qu, Qi Yang, Bingyin Shi & Peng Hou

  2. Department of Endocrinology, Xi’an Central Hospital, 710003, Xi’an, P. R. China

    Heng Li & Zhufang Tian

  3. Department of Endocrinology and Metabolism, The First Affiliated Hospital of China Medical University, 110001, Shenyang, P. R. China

    Haixia Guan

  4. Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi’an Jiaotong University, 710061, Xi’an, P. R. China

    Bingyin Shi & Peng Hou

  5. Center for Translational Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, 710061, Xi’an, P. R. China

    Meiju Ji

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  1. Heng Li
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Correspondence to Meiju Ji or Peng Hou.

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Li, H., Tian, Z., Qu, Y. et al. SIRT7 promotes thyroid tumorigenesis through phosphorylation and activation of Akt and p70S6K1 via DBC1/SIRT1 axis. Oncogene 38, 345–359 (2019). https://doi.org/10.1038/s41388-018-0434-6

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