Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation
Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation
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DOI：
10.1126/science.1137999
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发表时间：
2007-03-16
期刊：
影响因子：
56.9
通讯作者：
Bartel, David P.
中科院分区：
文献类型：
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作者：
Mayr, Christine;Hemann, Michael T.;Bartel, David P.
微小RNA（miRNAs）是类似于22个核苷酸的RNA，它们能够与信使RNA内的位点配对，以确定对这些信使RNA的转录后抑制。异常的miRNA表达可促进肿瘤发生，但众多miRNA - 靶标关系中哪些与这一过程相关尚不清楚。在此，我们报道先前与人类肿瘤相关的染色体易位破坏了let - 7 miRNA对高迁移率族蛋白A2（Hmga2）的抑制。这种被破坏的抑制促进了不依赖贴壁的生长，这是致癌转化的一个特征。因此，失去由miRNA介导的对癌基因的抑制为肿瘤发生提供了一种机制，并且破坏单个miRNA - 靶标相互作用可在哺乳动物细胞中产生一种可观察到的表型。
MicroRNAs ( miRNAs) are similar to 22-nucleotide RNAs that can pair to sites within messenger RNAs to specify posttranscriptional repression of these messages. Aberrant miRNA expression can contribute to tumorigenesis, but which of the many miRNA-target relationships are relevant to this process has been unclear. Here, we report that chromosomal translocations previously associated with human tumors disrupt repression of High Mobility Group A2 (Hmga2) by let-7 miRNA. This disrupted repression promotes anchorage-independent growth, a characteristic of oncogenic transformation. Thus, losing miRNA-directed repression of an oncogene provides a mechanism for tumorigenesis, and disrupting a single miRNA-target interaction can produce an observable phenotype in mammalian cells.