中国医科大学学报

中国医科大学学报

中国医科大学学报 ›› 2011, Vol. 40 ›› Issue (9): 777–.

• 护理学 •    下一篇

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

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   

  1. (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)
  • 出版日期:2011-09-30 发布日期:2012-03-07

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

LU Zhi-hua1,WANG Yong 2,3,CHI Chang-liang 1,3,TANG Yu-zhe 1,3,CAI Yong4,JIN Jing-ji4,WANG Chun-xi1   

  1. (1. The Urology Department,First Hospital of Jilin University,Changchun 130021,China;2. The Urology Department of Pelple Hospital of Jilin Province,Changchun 130021,China;3. The Postgraduate Institute of Jilin University,Changchun 130012,China;4. College of Life Science,Jilin University,Changchun130012,China)
  • Online:2011-09-30 Published:2012-03-07

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Fuhrman Ⅲ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Fuhrman Ⅲ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Fuhrman Ⅲ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Fuhrman Ⅲ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。

关键词: 组蛋白乙酰化, 肾透明细胞癌, hMOF, 组蛋白乙酰化, 肾透明细胞癌, hMOF

Abstract: 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 expres-sion level of hMOF in ccRCC tissue and peri-carcinoma normal renal tissue. IHC was used to investigate the acetylation levels of histone ly-sine 5,8,16(H4K5,H4K8,H4K16). One-way ANOVA and Fisher analyses were used to access the association between hMOF protein ex-pression and clinic data of ccRCC patients. Results qRT-PCR analysis in 9 ccRCC and their controls showed that hMOF mRNA downreg-ulated >2-fold in 44.4% (4/9)cases using mRNA from peri-carcinoma normal renal tissue and housekeeping gene CAPDH as reference.hMOF protein expression was markedly reduced in 39.4% cases (26/66),especially in Fuhrman Ⅲcases (69.2%,18/26). H4K5,H4K8acetylation 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 ⅢccRCC,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 clini-cal characteristics of ccRCC patients.

Key words: histone acetylation, renal cell carcinoma, hMOF, histone acetylation, renal cell carcinoma, hMOF

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[2] 宿佳,王雨桐,祁馨卉,李妍,吴迪,刘云鹏,姜又红. 氧化型甘露聚糖修饰的肿瘤细胞疫苗诱导CTL的抗肿瘤免疫效果评价[J]. 中国医科大学学报, 2015, 44(5): 420-424.
[3] 那磊,吴斌. NF?кB p65和HIF?1α在肾透明细胞癌中的表达及意义[J]. 中国医科大学学报, 2014, 43(6): 519-522.
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