Urology Department, The First Clinical Hospital, Jilin University, Changchun City, Jilin 130021, China.
J Exp Clin Cancer Res. 2013 Feb 9;32(1):8. doi: 10.1186/1756-9966-32-8.
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.
MYST1（也称为 hMOF）作为组蛋白乙酰转移酶（HATs）家族的成员，是一种表观遗传标记的活性基因，主要负责细胞中组蛋白 H4K16 的乙酰化。最近的研究表明，hMOF 的异常基因表达参与了某些原发性癌症。在这里，我们研究了 hMOF 表达和组蛋白 H4K16 乙酰化在原发性肾细胞癌（RCC）中的作用。同时，我们还研究了 hMOF 表达与 RCC 中透明细胞 RCC（ccRCC）标志物碳水化合物酶 IX（CA9）之间的相关性。
以冷冻的 RCC 组织和 RCC 细胞系为材料，采用逆转录聚合酶链反应（RT-PCR）、western blot 和免疫组织化学染色方法。
RT-PCR 结果表明，hMOF 基因在 90.5%（19/21）的 RCC 患者中表达水平经常下调。在 RCC 组织和 RCC 细胞系中 hMOF 蛋白的减少与组蛋白 H4K16 的乙酰化密切相关。此外，在 100%的 ccRCC 患者（21/21）中检测到 CA9 的过表达。然而，瞬时转染 hMOF 对 ccRCC 786-0 细胞中 CA9 的基因和蛋白表达均无影响。
hMOF 作为 H4K16 的乙酰转移酶可能参与了肾癌的发病机制，这种表观遗传变化可能是一种新的 CA9 独立的 RCC 诊断标志物。
