Loss of UHRF2 expression is associated with human neoplasia, promoter hypermethylation, decreased 5-hydroxymethylcytosine, and high proliferative activity.
Loss of UHRF2 expression is associated with human neoplasia, promoter hypermethylation, decreased 5-hydroxymethylcytosine, and high proliferative activity.
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DOI：
10.18632/oncotarget.12583
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发表时间：
2016-11-15
期刊：
影响因子：
--
通讯作者：
Hallstrom TC
中科院分区：
文献类型：
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作者：
Lu H;Bhoopatiraju S;Wang H;Schmitz NP;Wang X;Freeman MJ;Forster CL;Verneris MR;Linden MA;Hallstrom TC
具有PHD和环指结构域2（UHRF 2）的泛素样结合5-羟甲基胞嘧啶（5 hmC），这是一种参与组织发育的DNA碱基，但尚不清楚它们在正常和恶性人体组织中的分布如何相互比较。我们使用IHC对人类肿瘤标本（160例来自19种肿瘤类型）或正常组织进行检测，以确定UHRF 2、Ki-67和5 hmC的表达和分布。我们还检测了UHRF 2在脐带血祖细胞中的表达，并将其表达与6种白血病细胞系和15种原发性人类白血病的甲基化状态进行了比较。UHRF 2在大多数非肿瘤性分化组织中高度表达，与5 hmC平行，具有低Ki-67定义的增殖活性。UHRF 2在常见的淋巴样祖细胞和成熟淋巴细胞中表达，但在常见的髓样祖细胞或单核细胞中不表达。与此相反，在人类癌症组织中的UHRF 2免疫染色显示广泛的减少或异常的细胞质定位，这与较高的Ki-67和减少5 hmC。在一些白血病细胞系中UHRF 2表达降低，这与启动子高甲基化相关，并且在原发性人类白血病样品中观察到类似的UHRF 2甲基化谱。因此，UHRF 2和5 hmC广泛存在于分化的人类组织中，并且UHRF 2蛋白在多种人类癌症中表达不足或错误定位。
Ubiquitin-like with PHD and ring finger domains 2 (UHRF2) binds to 5-hydroxymethylcytosine (5hmC), a DNA base involved in tissue development, but it is unknown how their distribution compares with each other in normal and malignant human tissues. We used IHC on human tumor specimens (160 from 19 tumor types) or normal tissue to determine the expression and distribution of UHRF2, Ki-67, and 5hmC. We also examined UHRF2 expression in cord blood progenitors and compared its expression to methylation status in 6 leukemia cell lines and 15 primary human leukemias. UHRF2 is highly expressed, paralleling that of 5hmC, in most non-neoplastic, differentiated tissue with low Ki-67 defined proliferative activity. UHRF2 is expressed in common lymphoid progenitors and mature lymphocytes but not common myeloid progenitors or monocytes. In contrast, UHRF2 immunostaining in human cancer tissues revealed widespread reduction or abnormal cytoplasmic localization which correlated with a higher Ki-67 and reduced 5hmC. UHRF2 expression is reduced in some leukemia cell lines, this correlates with promoter hypermethylation, and similar UHRF2 methylation profiles are seen in primary human leukemia samples. Thus, UHRF2 and 5hmC are widely present in differentiated human tissues, and UHRF2 protein is poorly expressed or mislocalized in diverse human cancers.