Epigenetic change in kidney tumor: downregulation of histone acetyltransferase MYST1 in human renal cell carcinoma

J Exp Clin Cancer Res. 2013 Feb 9;32(1):8. doi: 10.1186/1756-9966-32-8.

Abstract

Background: MYST1 (also known as hMOF), a member of the MYST family of histone acetyltransferases (HATs) as an epigenetic mark of active genes, is mainly responsible for histone H4K16 acetylation in the cells. Recent studies have shown that the abnormal gene expression of hMOF is involved in certain primary cancers. Here we examined the involvement of hMOF expression and histone H4K16 acetylation in primary renal cell carcinoma (RCC). Simultaneously, we investigated the correlation between the expression of hMOF and clear cell RCC (ccRCC) biomarker carbohydrase IX (CA9) in RCC.

Materials and methods: The frozen RCC tissues and RCC cell lines as materials, the reverse transcription polymerase chain reaction (RT-PCR), western blotting and immunohistochemical staining approaches were used.

Results: RT-PCR results indicate that hMOF gene expression levels frequently downregulated in 90.5% of patients (19/21) with RCC. The reduction of hMOF protein in both RCC tissues and RCC cell lines is tightly correlated with acetylation of histone H4K16. In addition, overexpression of CA9 was detected in 100% of ccRCC patients (21/21). However, transient transfection of hMOF in ccRCC 786-0 cells did not affect both the gene and protein expression of CA9.

Conclusion: hMOF as an acetyltransferase of H4K16 might be involved in the pathogenesis of kidney cancer, and this epigenetic changes might be a new CA9-independent RCC diagnostic maker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Blotting, Western
  • Carcinoma, Renal Cell / enzymology*
  • Carcinoma, Renal Cell / genetics
  • Down-Regulation
  • Epigenesis, Genetic
  • Epigenomics
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Histone Acetyltransferases / genetics*
  • Histone Acetyltransferases / metabolism
  • Humans
  • Immunohistochemistry
  • Kidney Neoplasms / enzymology*
  • Kidney Neoplasms / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection

Substances

  • Biomarkers, Tumor
  • Histone Acetyltransferases
  • KAT8 protein, human