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

Yong Wang,Zhihua Lu,Chunxi Wang,Donglu Wu,Jingji Jin,Yong Cai,Rui Zhang,Wentao Sun

doi:10.1186/1756-9966-32-8

Abstract

BackgroundMYST1 (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 methodsThe 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.ResultsRT-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.ConclusionhMOF 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.

Highlights

Changes of chromatin structure are mainly regulated by epigenetic regulations including ATP-dependent remodeling of nucleosomes, the incorporation of variants histones into nucleosomes and posttranslational modifications of histones [1]
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 renal cell carcinoma (RCC) diagnostic maker
Downregulation of hMOF mRNA in primary renal cell carcinoma tissues In order to know whether the hMOF is involved in the pathogenesis of primary RCC or not, we first examined the mRNA levels of hMOF and other hypoxia signature genes including CA9, vascular endothelial growth factor (VEGF) and HIF1α in 4 random cases of newly diagnosed clear cell RCC (ccRCC) (Figure 1A) by reverse transcription PCR (RT-PCR) and quantitative real-time PCR

Summary

Introduction

Changes of chromatin structure are mainly regulated by epigenetic regulations including ATP-dependent remodeling of nucleosomes, the incorporation of variants histones into nucleosomes and posttranslational modifications of histones [1]. It has been reported that depletion of hMOF in human cells leads to genomic instability, spontaneous chromosomal aberrations, cell cycle defects, reduced transcription of certain genes, and defective DNA damage repair and early embryonic lethality [4,5,6,7]. This suggests a critical role for hMOF in fundamental processes such as gene transcription, cell proliferation, differentiation and DNA repair response. We investigated the correlation between the expression of hMOF and clear cell RCC (ccRCC) biomarker carbohydrase IX (CA9) in RCC

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