Department of Urology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China.
Institute of Urology of Hubei Province Wuhan China.
FEBS Open Bio. 2019 Feb 21;9(4):693-706. doi: 10.1002/2211-5463.12600. eCollection 2019 Apr.
Histone lysine methyltransferases (HMT) comprise a subclass of epigenetic regulators; dysregulation of these enzymes affects gene expression, which may lead to tumorigenesis. Here, we performed an integrated analysis of 50 HMTs in bladder cancer and found intrinsic links between copy number alterations, mutations, gene expression levels, and clinical outcomes. Through integrative analysis, we identified six HMT genes (,,,,, and ) that may play a key role in the development and progression of bladder cancer. Of these six HMTs, histone lysine -methyltransferase 2D () exhibited the highest mutation rate in bladder cancer. Our comparison of the mRNA and miRNA expression profiles of mutated and wild-type suggested that two signaling pathways (FOX1-miR-1224-5p-DLK1 and HIF/GATA5-miR-133a-3p-DRD5) may mediate the tumor suppressive effect of the mutation. In summary, our findings indicate that mutations in HMT genes, especially mutation, may play a role in the development of bladder cancer.
组蛋白赖氨酸甲基转移酶（HMT）属于表观遗传调控因子的一个亚类；这些酶的失调会影响基因表达，从而可能导致肿瘤发生。在这里，我们对膀胱癌中的 50 种 HMT 进行了综合分析，发现了拷贝数改变、突变、基因表达水平和临床结果之间的内在联系。通过综合分析，我们确定了六个可能在膀胱癌发生和发展中起关键作用的 HMT 基因（,,,,, 和 ）。在这六个 HMT 中，组蛋白赖氨酸甲基转移酶 2D（）在膀胱癌中的突变率最高。我们对突变型和野生型的 mRNA 和 miRNA 表达谱进行比较后发现，两条信号通路（FOX1-miR-1224-5p-DLK1 和 HIF/GATA5-miR-133a-3p-DRD5）可能介导了 突变的肿瘤抑制作用。总之，我们的研究结果表明，HMT 基因突变，尤其是 突变，可能在膀胱癌的发生中起作用。
