Abnormal Expressions of DNA Glycosylase Genes NEIL1, NEIL2, and NEIL3 Are Associated with Somatic Mutation Loads in Human Cancer.
Abnormal Expressions of DNA Glycosylase Genes NEIL1, NEIL2, and NEIL3 Are Associated with Somatic Mutation Loads in Human Cancer.
复制标题
DOI：
10.1155/2016/1546392
复制
发表时间：
2016
影响因子：
--
通讯作者：
Sugimura H
中科院分区：
文献类型：
--
作者：
Shinmura K;Kato H;Kawanishi Y;Igarashi H;Goto M;Tao H;Inoue Y;Nakamura S;Misawa K;Mineta H;Sugimura H
DNA糖基化酶NEIL 1、NEIL 2和NEIL 3的异常对人类癌症的影响尚未完全阐明。在本文中，我们发现，中位数体细胞总突变负荷和中位数体细胞单核苷酸突变负荷表现出显着的负相关性与NEIL 1和NEIL 2表达水平的中位数和显着的正相关性与NEIL 3表达水平的中位数使用癌症基因组图谱（TCGA）数据库中的13种癌症类型的数据。一部分癌症类型表现出NEIL 1和NEIL 2表达降低和NEIL 3表达升高，并且NEIL 1、NEIL 2和NEIL 3的这种异常表达也与癌症中的突变负荷显著相关。作为NEIL 1在癌症中表达减少的潜在机制，发现了通过启动子超甲基化的NEIL 1的表观遗传沉默。最后，我们研究了NEIL 3表达水平升高与癌症中体细胞突变数量增加相关的原因，发现NEIL 3表达与APOBEC 3B表达正相关，APOBEC 3B是一种有效的突变诱导剂，在多种癌症中。这些结果表明NEIL 1、NEIL 2和NEIL 3的异常表达通过与体细胞突变负荷相关而参与癌症。
The effects of abnormalities in the DNA glycosylases NEIL1, NEIL2, and NEIL3 on human cancer have not been fully elucidated. In this paper, we found that the median somatic total mutation loads and the median somatic single nucleotide mutation loads exhibited significant inverse correlations with the median NEIL1 and NEIL2 expression levels and a significant positive correlation with the median NEIL3 expression level using data for 13 cancer types from the Cancer Genome Atlas (TCGA) database. A subset of the cancer types exhibited reduced NEIL1 and NEIL2 expressions and elevated NEIL3 expression, and such abnormal expressions of NEIL1, NEIL2, and NEIL3 were also significantly associated with the mutation loads in cancer. As a mechanism underlying the reduced expression of NEIL1 in cancer, the epigenetic silencing of NEIL1 through promoter hypermethylation was found. Finally, we investigated the reason why an elevated NEIL3 expression level was associated with an increased number of somatic mutations in cancer and found that NEIL3 expression was positively correlated with the expression of APOBEC3B, a potent inducer of mutations, in diverse cancers. These results suggested that the abnormal expressions of NEIL1, NEIL2, and NEIL3 are involved in cancer through their association with the somatic mutation load.