UHRF1、β-TrCP1和HAUSP的表达与胶质瘤分级的相关性研究  

Study on the corelation between the expressions of β-TrCP1, UHRF1, HAUSP and the grade of glioma

作　　者：李玉辉[1] 陆丽娟 王磊[3] 张晓茹 胡万宁[4] 李玉凤[4] Li Yuhui;Lu Lijuan;Wang Lei;Zhang Xiaoru;Hu Wanning;Li Yufeng(Department of Neurosurgery,Tangshan People’s Hospital,Tangshan 063001,China;Graduate School of North China University of Science and Technology,Tangshan 063210,China;Department of Pathology,Tangshan People’s Hospital,Tangshan 063001,China;Cancer Institute,Tangshan People’s Hospital,Tangshan 063001,China)

机构地区：[1]唐山市人民医院神经外科,063001 [2]华北理工大学研究生院,唐山063210 [3]唐山市人民医院病理科,063001 [4]唐山市人民医院肿瘤研究所,063001

出　　处：《中华神经创伤外科电子杂志》2019年第6期325-329,共5页Chinese Journal Of Neurotraumatic Surgery：Electronic Edition

基　　金：唐山市科技创新团队培养计划(17130205D)

摘　　要：目的分析泛素样含PHD和环指域蛋白1(UHRF1)、β-转导重复相容蛋白1(β-Tr CP1)和疱疹病毒相关性泛素特异性蛋白酶(HAUSP)在胶质瘤组织中的表达及与临床病理特征的相关性。方法收集唐山市人民医院病理科自2011年6月至2015年5月经外科手术切除、石蜡包埋的胶质瘤组织共84例。采用免疫组织化学染色法检测UHRF1、β-Tr CP1和HAUSP在WHOⅠ~Ⅳ级胶质瘤中的表达情况,并分析各蛋白表达与临床病理特征的相关性。结果UHRF1、β-Tr CP1和HAUSP蛋白在Ⅰ~Ⅳ级胶质瘤组织中均表达。三者的蛋白阳性率均与胶质瘤患者的病理分级相关,UHRF1和HAUSP蛋白阳性率随着胶质瘤级别增高而增高(P=0.005、0.002),而β-Tr CP1的蛋白阳性率随着胶质瘤级别增高而降低(P=0.003)。I~Ⅳ级胶质瘤组织中UHRF1表达均与β-Tr CP1呈负相关(Ⅰ级:r=-0.903,P=0.000;Ⅱ级:r=-0.930,P=0.000;Ⅲ级:r=-0.895,P=0.000;Ⅳ级:r=-0.920,P=0.000),而均与HAUSP呈正相关(Ⅰ级:r=0.931,P=0.000;Ⅱ级:r=0.866,P=0.000;Ⅲ级:r=0.803,P=0.000;Ⅳ级:r=0.904,P=0.000)。结论胶质瘤细胞中泛素化酶β-Tr CP1可能通过负向调控UHRF1的蛋白稳定性起抑癌作用,泛素化酶HAUSP可能通过正向调控UHRF1的蛋白稳定性起促癌作用,为进一步阐明胶质瘤发生发展的表观遗传机制提供了基础依据和新思路。Objective To analyze the expressions of ubiquitin-like con-taining PHD ring finger 1(UHRF1),β-transducin repeat-containing protein 1(β-Tr CP1)and herpes associated ubiquitin specific proteas(HAUSP)in glioma tissue and their correlation with clinicopathological features.Methods A total of 84 cases of paraffin-embedded glioma tissue surgically resected were collected from Department of Pathology,Tangshan People’s Hospital from June 2011 to May 2015.The expressions of UHRF1,β-Tr CP1 and HAUSP in WHO gradeⅠ-Ⅳglioma tissue were detected by immunohistochemical staining,and the correlation of the protein expressions with the clinicopathological features was analyzed.The relationship was analyzed by Spearman rank correlation between UHRF1 andβ-Tr CP1,as well as HAUSP.Results HAUSP,β-Tr CP1 and UHRF1 were all expressed in gradeⅠ-Ⅳglioma tissue.The positive expression rates of these proteins were all associated with the glioma classification.The positive expression rates of UHRF1 and HAUSP increased with the grade of glioma(P=0.005,P=0.002,respectively).The positive expression rates ofβ-Tr CP1 decreased with the grade of glioma(P=0.003).In addition,UHRF1 expressions in gradeⅠ-Ⅳglioma were all negatively associated withβ-Tr CP1(gradeⅠ:r=-0.903,P=0.000;gradeⅡ:r=-0.930,P=0.000;gradeⅢ:r=-0.895,P=0.000;gradeⅣ:r=-0.920,P=0.000),and they were all positively associated with HAUSP(gradeⅠ:r=0.931,P=0.000;gradeⅡ:r=0.866,P=0.000;gradeⅢ:r=0.803,P=0.000;gradeⅣ:r=0.904,P=0.000).Conclusion These data suggest that ubiquitination enzymeβ-Tr CP1 could play an anti-cancer role in glioma by negatively regulating the stability of UHRF1 protein,while de-ubiquitination enzyme HAUSP could perform a tumor-promoting function by positively regulating the stability of UHRF1 protein.This provides a basis and new idea for further elucidate the epigenetic mechanism of gliomagenesis and development.

关 键 词：胶质瘤 泛素样含PHD和环指域蛋白1 β-转导重复相容蛋白1 疱疹病毒相关性泛素特异性蛋白酶 

分 类 号：R73[医药卫生—肿瘤]