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

Yong Wang12, Rui Zhang34, Donglu Wu34, Zhihua Lu1, Wentao Sun1, Yong Cai3, Chunxi Wang1* and Jingji Jin3*

Author Affiliations

1 Urology Department, The First Clinical Hospital, Jilin University, Changchun City, Jilin 130021, China

2 Urology Department, Jilin province People’s Hospital, , Changchun City, Jilin 130021, China

3 College of Life Science, Jilin University, Changchun City, Jilin 130012, China

4 Graduate School of Jilin University, Changchun City, Jilin 130012, China

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Journal of Experimental & Clinical Cancer Research 2013, 32:8  doi:10.1186/1756-9966-32-8

Published: 9 February 2013

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.

Keywords:
Renal cell carcinoma; hMOF; Carbonate anhydrase IX