Department of Human Genetics, Aarhus University, Denmark.
Biochem Biophys Res Commun. 2010 Jul 30;398(3):565-70. doi: 10.1016/j.bbrc.2010.06.119. Epub 2010 Jul 1.
NSD3/WHSC1L1 histone methyltransferase gene aberrations are observed in leukemia and in breast and lung carcinomas, suggesting that NSD3 is implicated in carcinogenesis. In this study we examined in human breast cancer cells the NSD3L isoform which contains the catalytic histone methyltransferase SET-domain. siRNA directed depletion of NSD3L followed by genome-wide microarray analysis identified NSD3L regulated genes which could be functionally linked to cellular signaling pathways such as cell growth, cell cycle, cell motility, transcription, and apoptosis. Notably up-regulated genes are the cell cycle regulators E2F2 and Arl2. In accordance with a function of NSD3L in cell cycle regulation NSD3L depletion resulted in an increase in the number of cells in the S and G2/M cell cycle phases. Moreover, NSD3L depletion increased the invasiveness of MDA-MB-231 breast cancer cells indicating that NSD3L normally restrain cellular metastatic potential. Together the presented data indicates that NSD3L is a candidate tumor suppressor.
NSD3/WHSC1L1 组蛋白甲基转移酶基因异常在白血病以及乳腺癌和肺癌中均有观察到，提示 NSD3 参与了肿瘤的发生。在本研究中，我们在人乳腺癌细胞中检测了含有催化组蛋白甲基转移酶 SET 结构域的 NSD3L 异构体。siRNA 介导的 NSD3L 耗竭，随后进行全基因组微阵列分析，鉴定了 NSD3L 调控的基因，这些基因可能与细胞信号通路（如细胞生长、细胞周期、细胞迁移、转录和凋亡）功能相关。值得注意的是上调的基因是细胞周期调控因子 E2F2 和 Arl2。与 NSD3L 在细胞周期调控中的功能一致，NSD3L 耗竭导致 S 和 G2/M 细胞周期阶段的细胞数量增加。此外，NSD3L 耗竭增加了 MDA-MB-231 乳腺癌细胞的侵袭性，表明 NSD3L 通常抑制细胞的转移潜力。综上所述，这些数据表明 NSD3L 是候选肿瘤抑制因子。
