DNA甲基转移酶3B4过表达与肾透明细胞癌之间的关联。
An association between overexpression of DNA methyltransferase 3B4 and clear cell renal cell carcinoma.
作者信息
Liu You, Sun Liantao, Fong Peter, Yang Jie, Zhang Zhuxia, Yin Shuihui, Jiang Shuyuan, Liu Xiaolei, Ju Hongge, Huang Lihua, Bai Jing, Gong Kerui, Yan Shaochun, Zhang Chunyang, Shao Guo
机构信息
Biomedicine Research Center and Basic Medical College, Baotou Medical College, Inner Mongolia, PRC.
Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
出版信息
Oncotarget. 2017 Mar 21;8(12):19712-19722. doi: 10.18632/oncotarget.14966.
It is well known that abnormal DNA methylations occur frequently in kidney cancer. However, it remains unclear exactly which types of DNA methyltransferases (DNMT) contribute to the pathologies of kidney cancers. In order to determine the functions of DNA methyltransferase in kidney tumorigenesis on the molecular level, we examined the mRNA expression levels of DNMT1, DNMT3A, DNMT3B, and DNMT3B variants in renal cell carcinoma tissue. Both mRNA and protein levels of DNMT3B4, a splice variant of DNMT3B, were increased in renal cell carcinoma tissue compared with adjacent control tissues. Additionally, Alu elements and long interspersed nuclear elements (LINE-1) were hypomethylated in renal cell carcinoma tissue. Meanwhile, methylation of the promoter for RASSF1A, a tumor suppressor gene, was moderately increased in renal cell carcinoma tissue, while RASSF1A expression was decreased. Thus, our data suggest that the overexpression of DNMT3B4 may play an important role in human kidney tumorigenesis through chromosomal instability and methylation of RASSF1A.
众所周知，异常的DNA甲基化在肾癌中频繁发生。然而，究竟哪些类型的DNA甲基转移酶（DNMT）导致了肾癌的病理过程仍不清楚。为了在分子水平上确定DNA甲基转移酶在肾肿瘤发生中的功能，我们检测了肾细胞癌组织中DNMT1、DNMT3A、DNMT3B和DNMT3B变体的mRNA表达水平。与相邻对照组织相比，DNMT3B的剪接变体DNMT3B4的mRNA和蛋白质水平在肾细胞癌组织中均升高。此外，Alu元件和长散在核元件（LINE-1）在肾细胞癌组织中发生低甲基化。同时，肿瘤抑制基因RASSF1A启动子的甲基化在肾细胞癌组织中适度增加，而RASSF1A的表达则降低。因此，我们的数据表明，DNMT3B4的过表达可能通过染色体不稳定和RASSF1A的甲基化在人类肾肿瘤发生中起重要作用。
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