SIRT1 suppresses pituitary tumor progression by downregulating PTTG1 expression

Oncol Rep. 2022 Aug;48(2):143. doi: 10.3892/or.2022.8354. Epub 2022 Jun 22.

Abstract

Although pituitary tumors are among the most common types of brain tumor, the underlying molecular mechanism of this disease remains obscure. To this end, the role of sirtuin 1 (SIRT1) in pituitary tumors was reported. The results of reverse transcription‑quantitative PCR and immunohistochemistry revealed that sirtuin 1 (SIRT1) expression was downregulated in the tumor tissues of patients with pituitary tumors. In vitro experiments of the present study demonstrated that SIRT1 upregulation suppressed pituitary tumor cell line growth, while SIRT1 downregulation demonstrated the opposite effect. Additionally, it was determined that the enzymatic activity of SIRT1 was required for its cellular function. A mechanistic experiment determined that SIRT1 negatively regulated pituitary tumor‑transforming gene 1 (PTTG1) expression through the deacetylation of histone (H)3 lysine (K)9ac at the promoter region of PTTG1. Moreover, H3K9ac levels at the PTTG1 promoter were determined to be an essential regulatory element for PTTG1 expression. Thus, it was concluded that the SIRT1/H3K9ac/PTTG1 axis contributed to pituitary tumor formation and may represent a potential therapeutic strategy.

Keywords: pituitary tumor; pituitary tumor‑transforming gene 1; proliferation; sirtuin 1.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Pituitary Neoplasms* / genetics
  • Pituitary Neoplasms* / metabolism
  • Securin / genetics
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism

Substances

  • Securin
  • SIRT1 protein, human
  • Sirtuin 1