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 fibroblasts, where the RNA facilitates viral replication. Here, we report that HCMV infection or treatment of ARPE-19 diploid epithelial cells with DNA-damaging agents, etoposide or zeocin, induces HSATII RNA expression, and a kinase-independent function of ATM is required for the induction. Additionally, various breast cancer cell lines growing in adherent, two-dimensional cell culture express HSATII RNA at different levels, and levels are markedly increased when cells are infected with HCMV or treated with zeocin. High levels of HSATII RNA expression correlate with enhanced migration of breast cancer cells, and knockdown of HSATII RNA reduces cell migration and the rate of cell proliferation. Our investigation links high expression of HSATII RNA to the DNA damage response, centered on a noncanonical function of ATM, and demonstrates a role for the satellite RNA in tumor cell proliferation and movement.

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，在肿瘤细胞中HSATII拷贝数增加与结肠癌的预后不良有关，在人巨细胞病毒（HCMV）感染的成纤维细胞中RNA促进病毒复制。在这里，我们报告说，HCMV感染或用DNA破坏剂，依托泊苷或zeocin治疗ARPE-19二倍体上皮细胞会诱导HSATII RNA表达，并且诱导所需的ATM激酶独立功能。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，并且当细胞感染HCMV或用Zeocin处理时，水平显着增加。HSATII RNA的高水平表达与乳腺癌细胞的迁移增强有关，而敲除HSATII RNA可以降低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，集中于ATM的非规范功能，并证明了卫星RNA在肿瘤细胞增殖和移动中的作用。