2. Academic Validation
  3. Inhibition of H3K4 demethylation induces autophagy in cancer cell lines

Inhibition of H3K4 demethylation induces autophagy in cancer cell lines

  • Biochim Biophys Acta Mol Cell Res. 2017 Dec;1864(12):2428-2437. doi: 10.1016/j.bbamcr.2017.08.005.
Zhen Wang 1,  Qiao-Yun Long 1,  Lin Chen 1,  Jia-Dong Fan 2,  Zhao-Ning Wang 2,  Lian-Yun Li 3,  Min Wu 4,  Xuefeng Chen 5
Affiliations

Affiliations

  • 1 Hubei Key Laboratory of Cell Homeostasis, China; Hubei Key Laboratory of Developmentally Originated Disease, China; Department of Biochemistry and Molecular Biology, China.
  • 2 Hubei Key Laboratory of Cell Homeostasis, China; Department of Biochemistry and Molecular Biology, China.
  • 3 Hubei Key Laboratory of Cell Homeostasis, China; Hubei Key Laboratory of Developmentally Originated Disease, China; Department of Biochemistry and Molecular Biology, China. Electronic address: lilianyun@whu.edu.cn.
  • 4 Hubei Key Laboratory of Cell Homeostasis, China; Hubei Key Laboratory of Developmentally Originated Disease, China; Department of Biochemistry and Molecular Biology, China. Electronic address: wumin@whu.edu.cn.
  • 5 Hubei Key Laboratory of Cell Homeostasis, China; Department of Genetics, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China. Electronic address: xfchen@whu.edu.cn.
PMID: 28800922 DOI: 10.1016/j.bbamcr.2017.08.005
Abstract

Epigenetic factors and related small molecules have emerged to be strongly involved in Autophagy process. Here we report that 2-PCPA and GSK-LSD1, two inhibitors of histone H3K4 demethylase KDM1A/LSD1, induce Autophagy in multiple mammalian cell lines. The two small molecules induce accumulation of LC3II, formation of autophagosome and autolysosome, and SQSTM1/p62 degradation. 2-PCPA treatment inhibits cell proliferation through cell cycle arrest but does not inducing cell death. Exogenous expression of KDM1A/LSD1 impaired the autophagic phenotypes triggered by 2-PCPA. The Autophagy induced by 2-PCPA requires LC3-II processing machinery. But depletion of BECN1 and ULK1 with siRNA did not affect the LC3-II accumulation triggered by 2-PCPA. 2-PCPA treatment induces the change of global gene expression program, including a series of autophagy-related genes, such as SQSTM1/p62. Taken together, our data indicate that KDM1A/LSD1 inhibitors induce Autophagy through affecting the expression of autophagy-related genes and in a BECN1-independent manner.

Keywords

2-PCPA; Autophagy; Epigenetic inhibitors; GSK-LSD1; KDM1A/LSD1.

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