MicroRNA responses to cellular stress
MicroRNA responses to cellular stress
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DOI：
10.1158/0008-5472.can-06-1894
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发表时间：
2006-11-15
期刊：
影响因子：
11.2
通讯作者：
Kelsey, Karl T.
中科院分区：
文献类型：
--
作者：
Marsit, Carmen J.;Eddy, Karen;Kelsey, Karl T.
最近的工作已经开始探索小的非编码RNA种类，特别是microRNA（miRNA），在分类人类肿瘤和指导胚胎发育方面的工具作用。这些研究表明，基本上所有研究的生物体中的发育程序都部分地由miRNA的不同表达设定，并且肿瘤形成的特征在于miRNA的表达改变。由于这些观察结果是相互关联的，我们研究了诱导发育异常和癌症的细胞暴露是否会改变miRNA。使用385个已知人类miRNAs的微阵列，我们研究了在各种条件或治疗下生长的人类淋巴母细胞。叶酸缺乏诱导了miRNA表达的显著整体增加。我们观察到在用γ射线照射的细胞中miRNA表达没有显著改变，而暴露于亚砷酸钠导致miRNA表达的整体增加。从这些阵列中鉴定出miRNA hsa-miR-222在叶酸缺乏条件下显著过表达，并且这一发现在叶酸摄入量低的个体的人外周血中得到体内证实。细胞miRNA表达谱的改变代表了叶酸缺乏和砷暴露的一种新的作用模式，miRNA表达的特异性改变可能是这些和其他对人类健康有严重影响的毒素的有力生物标志物。
Recent work has begun to explore the instrumental role that small noncoding RNA species, particularly microRNAs (miRNA), have both in classifying human tumors and in directing embryonic development. These studies suggest that developmental programs in essentially all organisms studied are set, in part, by varied expressions of miRNAs and that neoplasia is characterized by altered expression of miRNAs. Reasoning that these observations are linked, we examined whether cellular exposures that induce both developmental anomalies and cancer alter miRNAs. Using microarrays of 385 known human miRNAs, we studied human lymphoblastoid cells grown under various conditions or treatments. Folate deficiency induced a pronounced global increase in miRNA expression. We observed no significant alteration in miRNA expression in cells treated with gamma-irradiation, whereas exposure to sodium arsenite led to global increases in miRNA expression. The miRNA hsa-miR-222 was identified from these arrays as significantly overexpressed under folate-deficient conditions, and this finding was confirmed in vivo in human peripheral blood from individuals with low folate intake. Alterations to cellular miRNA expression profiles represent a novel mode of action of folate deprivation and arsenic exposure, and specific alterations in miRNA expression may be a powerful biomarker for these and other toxins with serious effects on human health.