Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Nature. 2010 Oct 21;467(7318):986-90. doi: 10.1038/nature09459.
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 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.
已有研究表明,miRNAs 及其加工酶的异常表达与多种生物学过程有关,包括原发性和转移性肿瘤,但这一现象的调控机制尚不清楚。在这里,我们发现 p53 家族成员 TAp63 可抑制肿瘤的发生和转移,并通过协调调控 Dicer 和 miR-130b 来抑制转移。缺乏 TAp63 的转移性小鼠和人类肿瘤中的 Dicer 表达水平极低,我们发现 Dicer 和 miR-130b 的表达调控对缺乏 TAp63 的细胞的转移潜能有显著影响。TAp63 与 Dicer 启动子结合并使其转录激活,表明 TAp63 可直接转录调控 Dicer。这些数据为 TAp63 通过协调 Dicer 和 miR-130b 的转录调控抑制肿瘤和转移提供了新的认识,并可能对 miRNA 调控的众多过程具有重要意义。