Growth arrest-specific transcript 5 associated snoRNA levels are related to p53 expression and DNA damage in colorectal cancer.
Growth arrest-specific transcript 5 associated snoRNA levels are related to p53 expression and DNA damage in colorectal cancer.
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DOI：
10.1371/journal.pone.0098561
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Castellano L
中科院分区：
文献类型：
--
作者：
Krell J;Frampton AE;Mirnezami R;Harding V;De Giorgio A;Roca Alonso L;Cohen P;Ottaviani S;Colombo T;Jacob J;Pellegrino L;Buchanan G;Stebbing J;Castellano L
生长停滞特异性转录物5基因（GAS5）编码一个长的非编码RNA（lncRNA）和宿主的一些小核仁RNA（snoRNA），最近已经牵连到多种细胞过程和癌症。在这里，我们研究DNA损伤，p53，和GAS5 snoRNA之间的关系，以进一步了解该位点在细胞存活和肿瘤发生中的潜在作用，在体内和体外。我们使用定量技术来分析DNA损伤对GAS5 snoRNA表达的影响，并评估癌细胞系和正常、癌前和恶性人类结直肠组织中p53和GAS5 snoRNA之间的关系，并使用生物学技术来提示这些snoRNA在DNA损伤反应中的潜在作用。 GAS5衍生的snoRNA表达诱导的DNA损伤在p53依赖的方式在结直肠癌细胞系和它们的水平不受DICER。此外，p53水平与结直肠组织中GAS5衍生的snoRNA表达密切相关。总之，这些数据表明，GAS5衍生的snoRNA是在p53的控制下，它们在介导p53对DNA损伤的反应中具有重要作用，这可能与它们在核糖体中的功能无关。我们认为，这些snoRNA没有被DICER加工形成具有microRNA（miRNA）样功能的较小snoRNA衍生的RNA，但它们的确切作用需要进一步评估。此外，由于GAS5宿主snoRNA通常在qPCR定量中用作内源性对照，我们表明它们在DNA损伤实验中用作管家基因可能导致不准确的结果。
The growth arrest-specific transcript 5 gene (GAS5) encodes a long noncoding RNA (lncRNA) and hosts a number of small nucleolar RNAs (snoRNAs) that have recently been implicated in multiple cellular processes and cancer. Here, we investigate the relationship between DNA damage, p53, and the GAS5 snoRNAs to gain further insight into the potential role of this locus in cell survival and oncogenesis both in vivo and in vitro. We used quantitative techniques to analyse the effect of DNA damage on GAS5 snoRNA expression and to assess the relationship between p53 and the GAS5 snoRNAs in cancer cell lines and in normal, pre-malignant, and malignant human colorectal tissue and used biological techniques to suggest potential roles for these snoRNAs in the DNA damage response. GAS5-derived snoRNA expression was induced by DNA damage in a p53-dependent manner in colorectal cancer cell lines and their levels were not affected by DICER. Furthermore, p53 levels strongly correlated with GAS5-derived snoRNA expression in colorectal tissue. In aggregate, these data suggest that the GAS5-derived snoRNAs are under control of p53 and that they have an important role in mediating the p53 response to DNA damage, which may not relate to their function in the ribosome. We suggest that these snoRNAs are not processed by DICER to form smaller snoRNA-derived RNAs with microRNA (miRNA)-like functions, but their precise role requires further evaluation. Furthermore, since GAS5 host snoRNAs are often used as endogenous controls in qPCR quantifications we show that their use as housekeeping genes in DNA damage experiments can lead to inaccurate results.
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Vogelstein, B
DOI：
10.1073/pnas.0906947106
发表时间：
2009-09-15
影响因子：
11.1
作者：
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通讯作者：
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