Up-regulation of major histocompatibility complex class I-related molecules A (MICA) induced by 5-aza-2'-deoxycytidine.
- Author:
Jin-feng WU
1
;
Gui-li ZENG
;
Wei SHEN
;
Mei YANG
;
Feng WANG
;
Lü TIAN
;
Xuan LI
;
Wen-yan HU
;
Xiao-ping LI
;
Hong REN
;
Kai-fu TANG
Author Information
- Publication Type:Journal Article
- MeSH: Ataxia Telangiectasia Mutated Proteins; Azacitidine; analogs & derivatives; pharmacology; Caffeine; pharmacology; Carcinoma, Hepatocellular; metabolism; Cell Cycle Proteins; antagonists & inhibitors; metabolism; Cell Line; Cell Membrane; metabolism; DNA Damage; DNA-Binding Proteins; antagonists & inhibitors; metabolism; Flow Cytometry; Hep G2 Cells; Hepatocytes; metabolism; Histocompatibility Antigens Class I; genetics; metabolism; Humans; Liver Neoplasms; metabolism; Protein-Serine-Threonine Kinases; antagonists & inhibitors; metabolism; RNA, Messenger; genetics; metabolism; RNA, Small Interfering; genetics; Reverse Transcriptase Polymerase Chain Reaction; Tumor Suppressor Proteins; antagonists & inhibitors; metabolism; Up-Regulation
- From: Chinese Journal of Hepatology 2009;17(9):675-678
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVEMajor histocompatibility complex class I C-related molecules A and B (MICA and MICB) are innate immune system ligands for the NKG2D receptor expressed by natural killer cells and activated CD8(+)T cells. Our previous study showed that 5-aza-2'-deoxycytidine (5-aza-dC), a DNA methyltransferase inhibitor, can induce the expression of MICB and sensitized cells to NKL-cell-mediated cytolysis. The aim of this study was to determine the expression level of MICA in HepG2 cells (an HCC cell line) and L02 cells ( a normal liver cell), and to investigate the effect of 5-aza-dC on MICA expression in HepG2 cells.
METHODSCells were treated with 5-aza-dC, caffeine and ATM-specific siRNA. The cell surface MICA protein on HepG2 cells and L02 cells was determined using flow cytometry. The mRNA level was detected using real time RT-PCR.
RESULTSMICA was undetectable on the surface of L02 cells, but was highly expressed on HepG2 cells. MICA expression was upregulated in response to 5-aza-dC treatment (P less than 0.05), and the upregulation of MICA was partially prevented by pharmacological or genetic inhibition of ataxia telangiectasia mutated (ATM) kinase (P less than 0.05).
CONCLUSIONOur data suggest that 5-aza-dC induces the expression of MICA by a DNA damage-dependent mechanism.
