Gitareja Kezia, Chelliah Shalini S, Sanij Elaine, Sandhu Shahneen, Kang Jian, Khot Amit
St. Vincent's Institute of Medical Research, Melbourne, VIC 3065, Australia.
Department of Medicine-St. Vincent's Hospital, University of Melbourne, Melbourne, VIC 3065, Australia.
Cancers (Basel). 2025 Jul 31;17(15):2534. doi: 10.3390/cancers17152534.
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.
核糖体生物合成是一个高度协调的多步骤过程,该过程组装负责将mRNA翻译成蛋白质的核糖体机制。它始于细胞核内一个特殊核仁区域中RNA聚合酶I(Pol I)转录47S核糖体RNA(rRNA)基因的限速步骤,随后是rRNA加工、修饰以及与核糖体蛋白和由Pol III产生的5S rRNA组装。然后核糖体亚基被输出到细胞质中形成功能性核糖体。这个过程受到PI3K/RAS/MYC致癌网络的严格调控,该网络在许多癌症中经常失调。结果,核糖体合成、mRNA翻译和蛋白质合成速率增加。越来越多的证据支持这样一种观点,即核糖体生物合成和mRNA翻译的失调在癌症发病机制中起关键作用,将核糖体定位为一个有前景的治疗靶点。在这篇综述中,我们总结了目前对癌症中核糖体生物合成失调和功能的理解,评估了核糖体靶向治疗的临床进展,并探索了在这个快速发展的领域中新兴的治疗干预靶点。
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