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SIRT6 inhibits colorectal cancer stem cell proliferation by targeting CDC25A

Wenguang Liu1,2, Manwu Wu3, Hechun Du3

  • 1Department of General Surgery, Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China.

Oncology Letters
|March 20, 2018
PubMed

Insights

Silent information regulator 6 (SIRT6) suppresses colorectal cancer stem cell proliferation by inhibiting cell division cycle 25A (CDC25A). Reduced SIRT6 expression in colorectal CSCs correlates with increased proliferation and colony formation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Silent information regulator 6 (SIRT6) is recognized as a tumor suppressor.
  • Its specific role in colorectal cancer stem cells (CSCs) is currently unknown.

Purpose of the Study:

  • To investigate the function of SIRT6 in colorectal CSCs.
  • To elucidate the molecular mechanisms underlying SIRT6's action in these cells.

Main Methods:

  • Quantitative analysis of SIRT6 expression in colorectal CSCs.
  • Overexpression of SIRT6 in colorectal CSCs.
  • Cell proliferation, colony formation, and cell cycle assays.
  • Chromatin immunoprecipitation (ChIP) to assess SIRT6 binding to the CDC25A promoter and histone acetylation.

Main Results:

  • SIRT6 expression is decreased in colorectal CSCs.
  • SIRT6 overexpression inhibits CSC proliferation, colony formation, and induces G0/G1 phase arrest.
  • SIRT6 directly targets the CDC25A promoter, reducing histone H3 lysine 9 acetylation and repressing CDC25A expression.

Conclusions:

  • SIRT6 acts as a tumor suppressor in colorectal CSCs.
  • SIRT6 inhibits colorectal CSC proliferation by epigenetically targeting CDC25A expression.
Keywords:
cancer stem cellscell cyclecell division cycle 25Acell proliferationsilent information regulator 6

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