肾透明细胞癌组织中组蛋白乙酰化酶hMOF的表达及其乙酰化位点的初步研究  

The Expression and Acetylation Sites of hMOF Histone Acetyltransferase in Clear Cell Renal Cell Carcinoma

作　　者：芦志华[1] 王勇[2,3] 迟长亮[1,3] 唐宇哲[1,3] 蔡勇[4] 金景姬[4] 王春喜[1] 

机构地区：[1]吉林大学第一医院泌尿外科,长春13002 [2]吉林省人民医院泌尿外科,长春130021 [3]吉林大学研究生院,长春130012 [4]吉林大学生命科学学院,长春130012

出　　处：《中国医科大学学报》2011年第9期777-780,共4页Journal of China Medical University

基　　金：国家自然科学基金资助项目(31070668)

摘　　要：目的探讨肾透明细胞癌组织中组蛋白乙酰化酶hMOF的表达水平及其乙酰化位点。方法采用荧光实时定量PCR和免疫组化方法研究hMOF基因及蛋白在肾透明细胞癌组织及癌旁正常肾组织中的表达水平,采用免疫组化方法初步探讨hMOF的乙酰化位点(即H4K5,H4K8,H4K16的乙酰化水平)。采用单因素多元方差分析明确hMOF蛋白表达水平与肾癌患者临床特点的关系。结果荧光实时定量PCR结果显示:44.4%(4/9)的肾癌病例中hMOF的mRNA水平下降超过2倍。免疫组化结果显示:39.4%(26/66)的肾癌病例中hMOF蛋白表达为阴性或弱阳性,其中69.2%(18/26)为FuhrmanⅢ级的肾癌,在此26例肾癌病例中,有76.9%(20/26)的肾癌病例H4K5、K8乙酰化水平显著降低,其中FuhrmanⅢ级的肾癌病例占80%(16/20);88.5%(23/26)的肾癌病例H4K16乙酰化水平显著降低,其中FuhrmanⅢ级的肾癌病例占78.3%(18/23)。hMOF蛋白表达水平为阴性或弱阳性的患者,其肿瘤直径、Fuhrman分级、pT分期、区域淋巴结及远处器官转移风险均显著高于对照组。结论肾透明细胞癌,尤其FuhrmanⅢ级的肾透明细胞癌组织中hMOF基因及蛋白表达水平显著下降。hMOF的乙酰化位点不仅是H4K16,还包括H4K5、K8,并且这3者的乙酰化水平与hMOF的表达水平呈正比。hMOF蛋白表达水平与肾癌的恶性程度、临床分期、远处转移的风险有关。Objective To investigate the expression and acetylation sites of hMOF in clear cell renal cell carcinoma（ccRCC）.Methods Quantitative real-time PCR（qRT-PCR） and immunohistochemistry（IHC） were used to evaluate the mRNA abundance and protein expression level of hMOF in ccRCC tissue and peri-carcinoma normal renal tissue.IHC was used to investigate the acetylation levels of histone lysine 5,8,16（H4K5,H4K8,H4K16）.One-way ANOVA and Fisher analyses were used to access the association between hMOF protein expression and clinic data of ccRCC patients.Results qRT-PCR analysis in 9 ccRCC and their controls showed that hMOF mRNA downregulated 2-fold in 44.4%（4/9） cases using mRNA from peri-carcinoma normal renal tissue and housekeeping gene GAPDH as reference.hMOF protein expression was markedly reduced in 39.4% cases（26/66）,especially in Fuhrman Ⅲ cases（69.2%,18/26）.H4K5,H4K8 acetylation levels were reduced markedly in 20 cases（76.9%,20/26）,and H4K16 acetylation level was also reduced markedly in 23（88.5%,23/26） of these 26 ccRCC cases.In lower hMOF expression group,tumor size,Fuhrman grade,pT stage,lymphonode and distant metastasis were significantlly different from control group（P 0.05）.Conclusion In ccRCC tissues,especial Fuhrman Ⅲ ccRCC,mRNA abundance and protein expression of hMOF were reduced markedly.Acetylation sites of hMOF included not only H4K16 but also H4K5 and H4K8.Decrease of acetylation level of these three sites followed with hMOF reduction.The expression level of hMOF was related to the clinical characteristics of ccRCC patients.

关 键 词：组蛋白乙酰化 肾透明细胞癌 hMOF 

分 类 号：R34[医药卫生—基础医学]