An association between overexpression of DNA methyltransferase 3B4 and clear cell renal cell carcinoma.
An association between overexpression of DNA methyltransferase 3B4 and clear cell renal cell carcinoma.
复制标题
DNA甲基转移酶3B4过度表达与透明细胞肾细胞癌之间的关联
DOI：
10.18632/oncotarget.14966
复制
发表时间：
2017-03-21
期刊：
影响因子：
--
通讯作者：
Shao G
中科院分区：
文献类型：
--
作者：
Liu Y;Sun L;Fong P;Yang J;Zhang Z;Yin S;Jiang S;Liu X;Ju H;Huang L;Bai J;Gong K;Yan S;Zhang C;Shao G
众所周知，异常DNA甲基化在肾癌中频繁发生。然而，目前还不清楚究竟是哪种类型的DNA甲基转移酶（DNMT）导致肾癌的病理学。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DNMT 1、DNMT 3A、DNMT 3B和DNMT 3B变体的mRNA表达水平。DNMT 3B剪接变异体DNMT 3B 4的mRNA和蛋白水平在肾细胞癌组织中均高于癌旁对照组织。此外，Alu元件和长散布核元件（LINE-1）在肾细胞癌组织中呈低甲基化。与此同时，RASSF 1A，一种肿瘤抑制基因，启动子甲基化，在肾细胞癌组织中中度增加，而RASSF 1A表达下降。因此，我们的数据表明，DNMT 3B 4的过表达可能通过染色体不稳定性和RASSF 1A甲基化在人类肾脏肿瘤发生中发挥重要作用。
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.