Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers
Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers
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DOI：
10.1073/pnas.0307323101
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发表时间：
2004-03-02
影响因子：
11.1
通讯作者：
Croce, CM
中科院分区：
文献类型：
--
作者：
Calin, GA;Sevignani, C;Croce, CM
大量微小的非编码RNA已被克隆并命名为microRNA（miRs）。最近，我们报道了位于13 q14的miR-15 a和miR-16 a在B细胞慢性淋巴细胞白血病患者中频繁缺失和/或下调，这种疾病的特征是生存率增加。为了在全基因组的基础上进一步研究miR在人类癌症中的可能参与，我们绘制了186个miR，并将它们的位置与以前报道的非随机遗传改变的位置进行了比较。在这里，我们表明，miR基因通常位于脆性位点，以及在最小的杂合性丢失区域，最小的扩增区域（最小扩增子），或共同的断点区域。总体而言，186个miR基因中有98个（52.5%）位于癌症相关基因组区域或脆性位点。此外，通过北方印迹，我们已经表明，位于缺失区域的几个miR在癌症样品中具有低水平的表达。这些数据提供了可能在癌症中起作用的miR基因的目录，并认为基因组中miR的完整互补可能广泛参与癌症。
A large number of tiny noncoding RNAs have been cloned and named microRNAs(miRs). Recently, we have reported that miR-15a and miR-16a, located at 13q14, are frequently deleted and/or down-regulated in patients with B cell chronic lymphocytic leukemia, a disorder characterized by increased survival. To further investigate the possible involvement of miRs in human cancers on a genome-wide basis, we have mapped 186 miRs and compared their location to the location of previous reported nonrandom genetic alterations. Here, we show that miR genes are frequently located at fragile sites, as well as in minimal regions of loss of heterozygosity, minimal regions of amplification (minimal amplicons), or common breakpoint regions. Overall, 98 of 186 (52.5%) of miR genes are in cancer-associated genomic regions or in fragile sites. Moreover, by Northern blotting, we have shown that several miRs located in deleted regions have low levels of expression in cancer samples. These data provide a catalog of miR genes that may have roles in cancer and argue that the full complement of miRs in a genome may be extensively involved in cancers.