Ribosome abnormalities and cancer : Understanding the role of ribosomal proteins (RPs) in tumorigenesis and p53 regulation

现在人们普遍认为，核糖体生物发生的中断触发了P53信号通路，并且在细胞系中的研究表明，几个RP在这个核糖体-P53信号通路中起着至关重要的作用。有趣的是，由RP基因突变引起的人类核糖体疾病通常表现为癌症易感性增加。然而，将RPS与P53调控联系起来的分子机制仍不清楚。为了研究RPS在p53调控和癌症中的作用，我们开展了斑马鱼组织特异性RP基因敲除模型的建立，这是一个强大的癌症模型系统。我们已经发现，利用Tol2转座酶系统可以有效地利用miRNA对组织特异性的RP基因进行敲除。这项技术将是开发和了解斑马鱼癌症的宝贵工具。

It is now widely accepted that disruption of ribosome biogenesis triggers a p53 pathway and studies in cell lines have shown that several RPs are crucial players in this ribosome-p53 signaling pathway. Interestingly, human ribosomal diseases caused due to mutations in RP genes often present with increased cancer susceptibility. However, the molecular mechanism that links RPs to p53 regulation remains unknown. To investigate the role of RPs in p53 regulation and cancer, we undertook the development of tissue-specific RP knockdown model in zebrafish, which is a powerful cancer model system. We have found that tissue specific knockdown of RP gene using miRNA can be effectively carried out using the Tol2 transposase system. This technique will be a valuable tool to develop and understand cancer in zebrafish.