1. Academic Validation
  2. ZMIZ1 Regulates Proliferation, Autophagy and Apoptosis of Colon Cancer Cells by Mediating Ubiquitin-Proteasome Degradation of SIRT1

ZMIZ1 Regulates Proliferation, Autophagy and Apoptosis of Colon Cancer Cells by Mediating Ubiquitin-Proteasome Degradation of SIRT1

  • Biochem Genet. 2024 Jan 12. doi: 10.1007/s10528-023-10573-9.
Min Huang 1 Junfeng Wang 2 Zhengrong Zhang 2 Xueliang Zuo 2
Affiliations

Affiliations

  • 1 Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical College, No.2 Zheshan West Road, Wuhu, 241000, Anhui, China. huangmindoc88@126.com.
  • 2 Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical College, No.2 Zheshan West Road, Wuhu, 241000, Anhui, China.
Abstract

There are nearly 1.15 million new cases of colon Cancer, as well as 586,858 deaths from colon Cancer worldwide in 2020. The aim of this study is to reveal whether ZMIZ1 can control the fate of colon Cancer cells and the mechanism by which it functions. Specific shRNA transfection was used to knock down the expression of ZMIZ1 in colon Cancer cell lines (HCT116 and HT29), and cell proliferation was detected using EdU and CCK-8 reagents, Apoptosis by flow cytometry, and Autophagy by western blot. The interaction of ZMIZ1 and SIRT1 was analyzed. Knockdown of ZMIZ1 significantly inhibited Autophagy and proliferation, and induced Apoptosis of HCT116 and HT29 cells. The mRNA level of SIRT1 was not affected by ZMIZ1 knockdown, but the protein level of SIRT1 was significantly decreased and the protein level of the SIRT1-specific substrate, acetylated FOXO3a, was reduced. Immunoprecipitation assays identified the interaction between SIRT1 and ZMIZ1 in HCT116 and HT29 cells. ZMIZ1 increased intracellular ubiquitination of SIRT1. Knockdown or pharmacological inhibition of SIRT1 neutralized the effects of ZMIZ knockdown on proliferation, Autophagy and Apoptosis in HCT116 and HT29 cells. ZMIZ1 may control the fate of colon Cancer cells through the SIRT1/FOXO3a axis. Targeting ZMIZ1 would be beneficial for the treatment of colon Cancer.

Keywords

Apoptosis; Autophagy; Colon cancer; FOXO3a; Proliferation; STIR1; ZMIZ1.

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