TAp63 suppresses metastasis through coordinate regulation of Dicer and miRNAs

Article

关键词: LI-FRAUMENI-SYNDROME;    P63 EXPRESSION;    P53;    CANCER;    P73;    MUTANT;    MICE;    PROGRESSION;    CARCINOMA;    FAMILY;   

DOI  :  10.1038/nature09459

来源: SCIE

【 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(1-6), 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 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.

【 授权许可】

Free