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TAp63 suppresses metastasis through coordinate regulation of Dicer and miRNAs

机译：TAp63通过调节Dicer和miRNA抑制转移

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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 of Dicer and miR-130b markedly affected the metastatic potential of cells lacking TAp63. TAp63 binds to and transactivates the Dicer promoter, demonstrating direct transcrip-tional 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.
机译：在包括原发性和转移性肿瘤在内的多种生物学过程中，已经报道了microRNA（miRNA）和控制其加工的酶的异常表达，但是目前尚不清楚其调控机制。在这里，我们显示p53家族成员TAp63抑制肿瘤发生和转移，并协调调节Dicer和miR-130b抑制转移。缺乏TAp63的转移性小鼠和人类肿瘤表达Dicer的水平非常低，我们发现Dicer和miR-130b表达的调节明显影响了缺乏TAp63的细胞的转移潜能。 TAp63结合并激活Dicer启动子，表明TAp63对Dicer的直接转录调控。这些数据通过Dicer和miR-130b的协调转录调控，提供了TAp63在肿瘤和转移抑制中的作用的新颖理解，并且可能对许多受miRNA调控的过程有影响。

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  • 来源
    《Nature》 |2010年第7318期|P.986-990|共5页
  • 作者

    Xiaohua Su; Deepavali Chakravarti; Min Soon Cho; Lingzhi Liu; Young Jin Gi; Yu-Li Lin; Marco L. Leung; Adel El-Naggar; Chad J. Creighton; Milind B. Suraokar; Ignacio Wistuba; Elsa R. Flores;

  • 作者单位

    Department of Molecular and Cellular Oncology, The University of Texas M.D.Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA;

    rnDepartment of Molecular and Cellular Oncology, The University of Texas M.D.Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA Graduate School of Biomedical Sciences, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA;

    rnDepartment of Molecular and Cellular Oncology, The University of Texas M.D.Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA Graduate School of Biomedical Sciences, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA;

    rnDepartment of Molecular and Cellular Oncology, The University of Texas M.D.Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA;

    rnDepartment of Molecular and Cellular Oncology, The University of Texas M.D.Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA;

    rnDepartment of Molecular and Cellular Oncology, The University of Texas M.D.Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA;

    rnDepartment of Molecular and Cellular Oncology, The University of Texas M.D.Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA;

    rnDepartment of Pathology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA;

    rnDan L Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA;

    rnDepartment of Pathology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA;

    rnDepartment of Pathology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA;

    rnDepartment of Molecular and Cellular Oncology, The University of Texas M.D.Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA Graduate School of Biomedical Sciences, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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