Related Experiment Video

Updated: Jun 10, 2025

Deacetylation Assays to Unravel the Interplay between Sirtuins SIRT2 and Specific Protein-substrates
14:32

Deacetylation Assays to Unravel the Interplay between Sirtuins SIRT2 and Specific Protein-substrates

Published on: February 27, 2016

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SIRT2 deacetylates and decreases the expression of FOXM1 in colon cancer

Baris Yildiz1, Ramazan Demirel2, Jonas J Staudacher3,4

  • 1Department of Physiology, Institute of Health Sciences, Kafkas University, Kars, Türkiye.

Journal of Biochemical and Molecular Toxicology
|October 19, 2024
PubMed

Insights

Deacetylation of FOXM1 by SIRT2 reduces its expression in colon cancer. Targeting SIRT2 offers a potential therapeutic strategy for colorectal cancer management.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Forkhead box M1 (FOXM1) is a key regulator in cell proliferation and is implicated in various cancers.
  • FOXM1 activity is modulated by post-translational modifications, including acetylation.
  • SIRT2 is a deacetylase that can influence protein function and expression.

Purpose of the Study:

  • To investigate the role of SIRT2 in regulating FOXM1 expression in colon cancer.
  • To determine if SIRT2-mediated deacetylation of FOXM1 impacts colon cancer progression.
  • To explore the therapeutic potential of targeting the SIRT2-FOXM1 interaction in colorectal cancer.

Main Methods:

  • Immunohistochemistry on 90 human colon cancer tissue microarrays to assess FOXM1 and SIRT2 expression.
  • Co-immunoprecipitation assays to evaluate SIRT2-FOXM1 interaction in colon cancer cells.
  • In vitro deacetylation assays to confirm SIRT2's effect on FOXM1.
  • SIRT2 overexpression and knockdown experiments in HCT116 cells.

Main Results:

  • SIRT2 physically interacts with FOXM1 and deacetylates it in vitro.
  • SIRT2 overexpression decreases FOXM1 expression, while SIRT2 knockdown increases it in colon cancer cells.
  • High SIRT2 expression is negatively correlated with FOXM1 staining in human colorectal cancer samples.
  • SIRT2 is expressed in a significant portion of colorectal cancers.

Conclusions:

  • SIRT2 deacetylates FOXM1, leading to decreased FOXM1 protein levels in colon cancer.
  • A negative association exists between SIRT2 and FOXM1 expression in clinical colorectal cancer samples.
  • Targeting SIRT2 activity with small molecule inhibitors presents a promising therapeutic avenue for colorectal cancer.
Keywords:
CRCFOXM1SirReal2deacetylationposttranslational regulationresveratrolsirtuin

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