Ferreira Daniela, Escudeiro Ana, Adega Filomena, Chaves Raquel
Laboratory of Cytogenomics and Animal Genomics, Department of Genetics and Biotechnology, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal.
BioISI - Biosystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisboa, Lisbon, Portugal.
Front Genet. 2019 Feb 12;10:101. doi: 10.3389/fgene.2019.00101. eCollection 2019.
Satellite ncRNAs are emerging as key players in cell and cancer pathways. Cancer-linked satellite DNA hypomethylation seems to be responsible for the overexpression of satellite non-coding DNAs in several tumors. is the major satellite DNA of and recently, its presence and transcription was described across Bilateria genomes. This satellite DNA is GC-rich and includes a CpG island, what is suggestive of transcription regulation via DNA methylation. In this work, it was studied for the first time the methylation profile in cat primary cells, in four passages of the cat tumor cell line FkMTp and in eight feline mammary tumors and the respective disease-free tissues. Contrary to what was expected, we found that in most of the tumor samples analyzed, DNA was not hypomethylated. Furthermore, in these samples the transcription of does not correlate with the methylation status. The use of a global demethylating agent, 5-Azacytidine, in cat primary cells caused an increase in the non-coding RNA levels. However, global demethylation in the tumor FkMTp cells only resulted in the increased levels of the small RNA fraction. Our data suggests that DNA methylation of is involved in the regulation of this satellite DNA, however, other mechanisms are certainly contributing to the transcriptional status of the sequence, specifically in cancer.
卫星非编码RNA正成为细胞和癌症信号通路中的关键角色。癌症相关的卫星DNA低甲基化似乎是几种肿瘤中卫星非编码DNA过表达的原因。是……的主要卫星DNA，最近，其在两侧对称动物基因组中的存在和转录情况得到了描述。这种卫星DNA富含GC，包含一个CpG岛，这表明其通过DNA甲基化进行转录调控。在这项研究中，首次研究了猫原代细胞、猫肿瘤细胞系FkMTp的四代细胞以及八个猫乳腺肿瘤及其相应的无病组织中的……甲基化情况。与预期相反，我们发现在大多数分析的肿瘤样本中，……DNA并未发生低甲基化。此外，在这些样本中，……的转录与甲基化状态无关。在猫原代细胞中使用全局去甲基化剂5-氮杂胞苷会导致……非编码RNA水平升高。然而，肿瘤FkMTp细胞中的全局去甲基化仅导致……小RNA组分水平升高。我们的数据表明，……的DNA甲基化参与了这种卫星DNA的调控，然而，其他机制肯定也对该序列的转录状态有贡献，尤其是在癌症中。
