Induction of MHC class I-related chain B (MICB) by 5-aza-2'-deoxycytidine.
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.
Tang
Kai-Fu
KF
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, Chongqing, PR China. tangkaifu@hotmail.com
He
Cai-Xia
CX
Zeng
Gui-Li
GL
Wu
Jinfeng
J
Song
Guan-Bin
GB
Shi
Yi-Song
YS
Zhang
Wei-Guang
WG
Huang
Ai-Long
AL
Steinle
Alexander
A
Ren
Hong
H
D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004249:DNA Damage; D019175:DNA Methylation / Q000187:drug effects; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors*; D000077209:Decitabine; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011971:Receptors, Immunologic / Q000378:metabolism; D055607:Receptors, Natural Killer Cell; D014158:Transcription, Genetic / Q000187:drug effects
D004791:Enzyme Inhibitors; D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; C098080:MICB antigen; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine