Noncoding Centromeric RNA Expression Impairs Chromosome Stability in Human and Murine Stem Cells
Noncoding Centromeric RNA Expression Impairs Chromosome Stability in Human and Murine Stem Cells
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DOI：
10.1155/2017/7506976
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发表时间：
2017-01-01
期刊：
影响因子：
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通讯作者：
Monaco, Zoia L.
中科院分区：
文献类型：
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作者：
Chan, David Y. L.;Moralli, Daniela;Monaco, Zoia L.
我们分析了转录的非编码RNA着丝粒卫星对正常人和小鼠干细胞和纤维肉瘤细胞染色体分离的影响。在所有细胞系中，不同的着丝粒α DNA的过表达诱导了染色体在后期错误分离的显着增加。着丝粒小鼠小卫星的过表达也增加了小鼠干细胞的染色体不稳定性，但在人类细胞中没有。体内染色体分离分析表明，有丝分裂进程中的干扰，这是经常未解决的。活细胞成像显示，着丝粒卫星的过度表达导致细胞核中出现几种不同的染色体形态错误。我们的研究结果与其他报道相关，即在不同的癌细胞中检测到几种着丝粒非编码RNA，它们的表达导致分离错误。我们的研究进一步揭示了人类和小鼠细胞中基因组不稳定性的新来源。最近的研究表明，非编码着丝粒RNA存在于某些形式的癌症中，因此，几种类型的着丝粒非编码RNA的过表达可能是有用的作为肿瘤细胞的特异性标记。
We analyzed the effect of transcribed noncoding RNA centromeric satellites on chromosome segregation in normal human and murine stem and fibrosarcoma cells. The overexpression of different centromeric alphoid DNAs in all cell lines induced a marked increase in chromosome mis-segregation in anaphase. Overexpression of centromeric mouse minor satellite also increased chromosome instability in the murine stem but not in human cells. Analysis of chromosome segregation in vivo showed disturbances in the mitotic progression, which was frequently unresolved. Live cell imaging revealed that overexpression of centromeric satellites resulted in several different chromosomal morphological errors in the cell nuclei. Our findings correlated with other reports that several centromeric noncoding RNAs are detected in different carcinoma cells and their expression resulted in segregation errors. Our study furnishes further insights into a novel source of genomic instability in human and murine cells. It has recently been shown that noncoding centromeric RNAs are present in some form of cancer, and thus, overexpression of several types of centromeric noncoding RNAs may be useful as a specific maker for neoplastic cells.