CD1d induction in solid tumor cells by histone deacetylase inhibitors through inhibition of HDAC1/2 and activation of Sp1
Journal
Epigenetics
Journal Volume
7
Journal Issue
4
Pages
390-399
Date Issued
2012
Author(s)
Abstract
CD1d is a MHC class-like molecule that presents glycolipids to natural killer T (NKT) cells, then regulating innate and adaptive immunity. The regulation of CD1d gene expression in solid tumors is still largely unknown. Gene expression can be epigenetically regulated by DNA methylation and histone acetylation. We found that histone deacetylase inhibitors, trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA), induced CD1d gene expression in human (A549 and NCI-H292) and mouse (TC-1 and B16/F0) cancer cells. Simultaneous knockdown of HDAC1 and 2 induced CD1d gene expression. Sp1 inhibitor mitramycin A (MTM) blocked TSA- and SAHA-induced CD1d mRNA expression and Sp1 luciferase activity. Co-transfection of GAL4-Sp1 and Fc-luciferase reporters demonstrated that TSA and SAHA induced Sp1 luciferase reporter activity by enhancing Sp1 transactivation activity. The binding of Sp1 to CD1d promoter and histone H3 acetylation on Sp1 sites were increased by TSA and SAHA. These results indicate that TSA and SAHA could upregulate CD1d expression in tumor cells through inhibition of HDAC1/2 and activation of Sp1. ? 2012 Landes Bioscience.
Subjects
CD1d; Histone deacetylase inhibitor; Sp1
SDGs
Other Subjects
CD1d antigen; histone deacetylase 1; histone deacetylase 2; histone H3; messenger RNA; mithramycin; small interfering RNA; transcription factor Sp1; trichostatin A; vorinostat; animal cell; article; cancer immunotherapy; chromatin immunoprecipitation; controlled study; enzyme inhibition; gene silencing; histone acetylation; human; human cell; mouse; nonhuman; protein binding; protein expression; solid tumor; transcription initiation; tumor cell
Type
journal article