TAp63通过协同调控Dicer和miRNA抑制癌症转移

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TAp63 suppresses metastasis through coordinateregulation of Dicer and miRNAs
TAp63通过协同调控Dicer和miRNA抑制癌症转移
NatureVolume:467,Pages:986–990Date published21 October 2010)

中文摘要：许多研究中发现miRNA以及miRNA合成过程中的关键酶在多种癌症发生过程中出现异常。本文分析了P63，它是一个P53家族成员，抑制肿瘤的形成和转移，它能协同调控Dicer和miR-130b的表达，进而参与了肿瘤的转移。由于缺乏P63而导致肿瘤发生转移的人和鼠模型中，Dicer表达量很低，此外，当改变Dicer和miR-130b的表达时，能够显著的影响缺乏P63的细胞的转移潜能。P63能直接绑定并反式激活Dicer启动子，暗示了P63对Dicer的直接调控作用。这些结果都表明P63通过协同调控Dicer和miR-130b进而参与调节肿瘤的转移和形成过程。
英文摘要：Aberrant expression of microRNAs (miRNAs) and the enzymes that control their processing have been reported in multiple biological processes including primary and metastatic tumours, but the mechanisms governing this are not clearly understood. Here we show that TAp63, a p53 family member, suppresses tumorigenesis and metastasis, and coordinately regulates Dicer and miR-130b to suppress metastasis. Metastatic mouse and human tumours deficient in TAp63 express Dicer at very low levels, and we found that modulation of expression ofDicer andmiR-130b markedly affected the metastatic potential of cells lackingTAp63. TAp63 binds to and transactivates the Dicer promoter, demonstrating direct transcriptional regulation of Dicer by TAp63. These data provide a novel understanding of the roles of TAp63 in tumour and metastasis suppression through the coordinate transcriptional regulation of Dicer and miR-130b and may have implications for the many processes regulated by miRNAs.
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