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Association of SIRT1 and tumor suppressor gene TAp63 expression in head and neck squamous cell carcinoma

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Tumor Biology

Abstract

Expression of the protein deacetylase SIRT1 is associated with either poor or favorable prognosis in cancer patients, depending on the cancer type. In head and neck squamous cell carcinoma (HNSCC), SIRT1 expression is associated with favorable prognosis. However, the molecular mechanism underlying the tumor-suppressive function of SIRT1 in HNSCC is unknown. SIRT1 promotes differentiation in epithelial cells; therefore, we investigated whether SIRT1 promotes differentiation in HNSCC cells by studying the correlations between the expression of SIRT1 and several genes implicated in stemness or differentiation in HNSCC-derived cell lines. Our results suggest that SIRT1 does not contribute to differentiation in HNSCC cells. RNA interference-mediated reduction of SIRT1 revealed that SIRT1 supports the expression of TAp63, which has been implicated in tumor suppression, in addition to epithelial differentiation. A positive correlation was observed between SIRT1 and TAp63 expression in HNSCC tissues, as determined by quantitative reverse transcription-polymerase chain reaction analysis of RNA extracted from formalin-fixed paraffin-embedded biopsy samples. Together, these results suggest that although SIRT1 does not regulate differentiation of HNSCC cells, it functions as a tumor suppressor in HNSCC by supporting the transcription of tumor-suppressive TAp63. This finding supports the notion that SIRT1-activating drugs could be useful for the treatment of HNSCC.

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Acknowledgments

The authors would like to thank Mitsuyo Yoshihara (Kanagawa Cancer Center Research Institute) for the assistance in RNA extraction from FFPE samples. This study was partly supported by a Grant-in-Aid for Scientific Research to KK (24593034) from the Ministry of Education, Science, Sports, and Culture.

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Author notes

  1. Yasuo Takano

    Present address: School of Health Sciences, Tokyo University of Technology, Tokyo, Japan

Authors and Affiliations

  1. Molecular Cell Biology Division, Kanagawa Cancer Center Research Institute, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan

    Keiji Kikuchi, Rika Kasajima, Daisuke Hoshino, Naohiko Koshikawa & Yasuo Takano

  2. Department of Pathology, Kanagawa Cancer Center, Yokohama, Japan

    Akira Noguchi & Tomoyuki Yokose

  3. Molecular Pathology Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan

    Yohei Miyagi

  4. Department of Head and Neck Cancer, Kanagawa Cancer Center, Yokohama, Japan

    Akira Kubota

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  1. Keiji Kikuchi
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Correspondence to Keiji Kikuchi.

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Supplementary Figure 1

Semi-quantitative analysis of the effect of SIRT1 reduction on the expression of genes involved in the differentiation and maintenance of stemness in KOSC2 cells. Right panels show densitometry results of western blot analysis of SIRT1 or RT-PCR products normalized relative to G3PDH as 1. (JPEG 459 kb)

Supplementary Table 1

Quantification of gene expression in HNSCC cell lines shown in Figure 1. (DOCX 74 kb)

Supplementary Table 2

Clinicopathological parameters of 20 HNSCC biopsy samples analyzed in this study. (DOCX 72 kb)

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Kikuchi, K., Noguchi, A., Kasajima, R. et al. Association of SIRT1 and tumor suppressor gene TAp63 expression in head and neck squamous cell carcinoma. Tumor Biol. 36, 7865–7872 (2015). https://doi.org/10.1007/s13277-015-3515-y

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