CD1d induction in solid tumor cells by histone deacetylase inhibitors through inhibition of HDAC1/2 and activation of Sp1

Pei Ming Yang, Pei Jie Lin, Ching Chow Chen

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)390-399
Number of pages10
JournalEpigenetics
Volume7
Issue number4
Publication statusPublished - Apr 2012
Externally publishedYes

Fingerprint

trichostatin A
Histone Deacetylase Inhibitors
Luciferases
Neoplasms
Acetylation
Gene Expression
Histones
Plicamycin
Natural Killer T-Cells
Glycolipids
Gene Expression Regulation
Adaptive Immunity
DNA Methylation
Innate Immunity
Transcriptional Activation
Transfection
Up-Regulation
vorinostat
Messenger RNA

Keywords

  • CD1d
  • Histone deacetylase inhibitor
  • Sp1

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

CD1d induction in solid tumor cells by histone deacetylase inhibitors through inhibition of HDAC1/2 and activation of Sp1. / Yang, Pei Ming; Lin, Pei Jie; Chen, Ching Chow.

In: Epigenetics, Vol. 7, No. 4, 04.2012, p. 390-399.

Research output: Contribution to journalArticle

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