Pericentromeric human satellite II (HSATII) repeats are normally silent, but can be actively transcribed in tumor cells, where increased HSATII copy number is associated with a poor prognosis in colon cancer, and in human cytomegalovirus (HCMV)-infected cells, where the RNA facilitates viral replication. Here, we report that HCMV infection or treatment of ARPE-19 diploid epithelial cells with the DNA-damaging agents, etoposide and zeocin, induced HSATII RNA expression, and a kinase-independent function of ATM was required for the induction. Additionally, various breast cancer cell lines growing in adherent, 2-dimensional cell culture expressed HSATII RNA at different levels, and levels were markedly increased when cells were either infected with HCMV or treated with zeocin. High levels of HSATII RNA expression correlated with enhanced migration of breast cancer cells, and knockdown of HSATII RNA reduced cell migration and the rate of cell proliferation. Our investigation links high expression of HSATII RNA to the DNA damage response, centered on a non-canonical function of ATM, and demonstrates a role for the satellite RNA in tumor cell proliferation and movement.

中文翻译：

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HSATII RNA通过非经典的ATM调控的DNA损伤应答途径诱导，并促进肿瘤细胞的增殖和移动

人肠周围的人类卫星II（HSATII）重复通常是沉默的，但可以在肿瘤细胞中积极转录，其中HSATII拷贝数增加与结肠癌的预后差有关，在人巨细胞病毒（HCMV）感染的细胞中，RNA促进病毒复制。在这里，我们报告说，HCMV感染或ARPE-19二倍体上皮细胞的DNA破坏剂，依托泊苷和Zeocin的治疗，诱导的HSATII RNA表达以及ATM的激酶非依赖性功能是诱导所必需的。另外，在贴壁的二维细胞培养物中生长的各种乳腺癌细胞系以不同水平表达HSATII RNA，并且当细胞被HCMV感染或用Zeocin处理时，水平显着增加。高水平的HSATII RNA表达与乳腺癌细胞迁移增强相关，而敲低HSATII RNA则降低了细胞迁移和细胞增殖速率。我们的研究将HSATII RNA的高表达与DNA损伤反应联系起来，以ATM的非经典功能为中心，并证明了卫星RNA在肿瘤细胞增殖和运动中的作用。