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Induction of MHC class I-related chain B (MICB) by 5-aza-2'-deoxycytidine
Authors:Tang Kai-Fu  He Cai-Xia  Zeng Gui-Li  Wu Jinfeng  Song Guan-Bin  Shi Yi-Song  Zhang Wei-Guang  Huang Ai-Long  Steinle Alexander  Ren Hong
Affiliation:a Key Laboratory of Molecular Biology for Infectious Diseases of the State Ministry of Education, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, 74# Linjiang Road, Chongqing 400010, PR China
b Key Laboratory for Biomechanics and Tissue Engineering of the State Ministry of Education, Chongqing University, Chongqing 400044, PR China
c Department of Immunology, Institute for Cell Biology, Eberhard-Karls University Tubingen, 72076 Tubingen, Germany
Abstract:5-Aza-2′-deoxycytidine (5-aza-dC), a DNA methyltransferase inhibitor, exerts antitumor activity through induction of cell cycle arrest, apoptosis and DNA damage. In this study, we showed that MHC class I-related chain B (MICB), a ligand of the NKG2D receptor expressed by natural killer cells and activated CD8(+) T cells, was upregulated following 5-aza-dC treatment. The upregulation of MICB was accompanied by promoter DNA demethylation and DNA damage. Furthermore, the upregulation of MICB was partially prevented by pharmacological or genetic inhibition of ataxia telangiectasia mutated (ATM) kinase. Our results suggest that promoter DNA demethylation, in combination with DNA damage, contribute to the upregulation of MICB induced by 5-aza-dC.
Keywords:5-Aza-dC   DNA damage   DNA methyltransferase inhibitor   MICB
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