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

Epigenetic change in kidney tumor: downregulation of histone acetyltransferase MYST1 in human renal cell carcinoma.
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DOI:
10.1186/1756-9966-32-8
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发表时间:
2013-02-09
期刊:
Journal of experimental & clinical cancer research : CR
影响因子:
--
通讯作者:
Jin J
Jin J
中科院分区:
其他
文献类型:
--
作者:
Wang Y;Zhang R;Wu D;Lu Z;Sun W;Cai Y;Wang C;Jin J

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MYST 1(也称为hMOF)是组蛋白乙酰基转移酶(HATs)MYST家族的成员,作为活性基因的表观遗传标记,主要负责细胞中组蛋白H4 K16的乙酰化。最近的研究表明,hMOF基因的异常表达与某些原发性肿瘤有关。在此,我们研究了hMOF表达和组蛋白H4 K16乙酰化在原发性肾细胞癌(RCC)中的作用。同时,我们研究了hMOF和透明细胞RCC(ccRCC)生物标志物糖酶IX(CA 9)在RCC中的表达之间的相关性。以冰冻肾细胞癌组织和肾癌细胞系为材料,采用逆转录聚合酶链反应(RT-PCR)、免疫印迹和免疫组化染色方法。RT-PCR结果显示90.5%(19/21)的肾细胞癌患者hMOF基因表达下调。RCC组织和RCC细胞系中hMOF蛋白的减少与组蛋白H4 K16的乙酰化密切相关。此外,在100%的ccRCC患者中检测到CA 9过表达(21/21)。然而,hMOF在ccRCC 786-0细胞中的瞬时转染不影响CA 9的基因和蛋白表达。hMOF作为H4 K16的乙酰转移酶可能参与了肾癌的发病过程,这种表观遗传学改变可能成为一种新的非CA 9依赖性肾癌诊断标志物。
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. 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. 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. 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.
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