文章：

核糖体生物合成与功能在癌症中的作用：从机制到治疗

Ribosome Biogenesis and Function in Cancer: From Mechanisms to Therapy

原文发布日期：31 July 2025

DOI: 10.3390/cancers17152534

类型: Article

开放获取: 是

英文摘要：

Ribosome biogenesis is a highly coordinated, multi-step process that assembles the ribosomal machinery responsible for translating mRNAs into proteins. It begins with the rate-limiting step of RNA polymerase I (Pol I) transcription of the 47S ribosomal RNA (rRNA) genes within a specialised nucleolar region in the nucleus, followed by rRNA processing, modification, and assembly with ribosomal proteins and the 5S rRNA produced by Pol III. The ribosomal subunits are then exported to the cytoplasm to form functional ribosomes. This process is tightly regulated by the PI3K/RAS/MYC oncogenic network, which is frequently deregulated in many cancers. As a result, ribosome synthesis, mRNA translation, and protein synthesis rates are increased. Growing evidence supports the notion that dysregulation of ribosome biogenesis and mRNA translation plays a pivotal role in the pathogenesis of cancer, positioning the ribosome as a promising therapeutic target. In this review, we summarise current understanding of dysregulated ribosome biogenesis and function in cancer, evaluate the clinical development of ribosome targeting therapies, and explore emerging targets for therapeutic intervention in this rapidly evolving field.

摘要翻译： 

核糖体生物发生是一个高度协调的多步骤过程，负责组装将mRNA翻译为蛋白质的核糖体机器。该过程始于细胞核内特化核仁区域中RNA聚合酶I（Pol I）对47S核糖体RNA（rRNA）基因进行转录的限速步骤，随后进行rRNA加工、修饰，并与核糖体蛋白及Pol III合成的5S rRNA组装。形成的核糖体亚基随后被转运至细胞质形成功能性核糖体。这一过程受到PI3K/RAS/MYC致癌网络的严格调控，该网络在多种癌症中常出现失调，导致核糖体合成、mRNA翻译及蛋白质合成速率显著提升。越来越多的证据表明，核糖体生物发生与mRNA翻译的失调在癌症发病机制中起着关键作用，使核糖体成为极具潜力的治疗靶点。本综述总结了当前对癌症中核糖体生物发生与功能失调的认识，评估了靶向核糖体治疗的临床研发进展，并探讨了这一快速发展领域中新兴的治疗干预靶点。

原文链接：

Ribosome Biogenesis and Function in Cancer: From Mechanisms to Therapy