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探讨核糖体 RNA 修饰在癌症中的作用。

Exploring the role of ribosomal RNA modifications in cancer.

机构信息

Centro de Investigación del Cáncer and Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC) - University of Salamanca, 37007 Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Hospital Universitario de Salamanca, 37007 Salamanca, Spain. Electronic address: https://twitter.com/@judithlopezluis.

Centro de Investigación del Cáncer and Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC) - University of Salamanca, 37007 Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Hospital Universitario de Salamanca, 37007 Salamanca, Spain.

出版信息

Curr Opin Genet Dev. 2024 Jun;86:102204. doi: 10.1016/j.gde.2024.102204. Epub 2024 May 17.

DOI:10.1016/j.gde.2024.102204
PMID:38759459
Abstract

Recent advances have highlighted the significant roles of post-transcriptional modifications in rRNA in various cancers. Evidence suggests that dysregulation of rRNA modifications acts as a common denominator in cancer development, with alterations in these modifications conferring competitive advantages to cancer cells. Specifically, rRNA modifications modulate protein synthesis and favor the specialized translation of oncogenic programs, thereby contributing to the formation of a protumorigenic proteome in cancer cells. These findings reveal a novel regulatory layer mediated by changes in the deposition of rRNA chemical modifications. Moreover, inhibition of these modifications in vitro and in preclinical studies demonstrates potential therapeutic applications. The recurrence of altered rRNA modification patterns across different types of cancer underscores their importance in cancer progression, proposing them as potential biomarkers and novel therapeutic targets. This review will highlight the latest insights into how post-transcriptional rRNA modifications contribute to cancer progression and summarize the main developments and ongoing challenges in this research area.

摘要

近年来的研究进展强调了转录后修饰在各种癌症中的重要作用。有证据表明,rRNA 修饰的失调是癌症发展的共同特征,这些修饰的改变赋予了癌细胞竞争优势。具体而言,rRNA 修饰调节蛋白质合成,并有利于致癌程序的专门翻译,从而促进癌细胞中致癌蛋白质组的形成。这些发现揭示了一种由 rRNA 化学修饰沉积变化介导的新型调控层。此外,在体外和临床前研究中抑制这些修饰表明了它们具有潜在的治疗应用。不同类型癌症中改变的 rRNA 修饰模式的复发突出了它们在癌症进展中的重要性,提出它们作为潜在的生物标志物和新的治疗靶点。这篇综述将强调最新的研究进展,阐述转录后 rRNA 修饰如何促进癌症的发展,并总结这一研究领域的主要进展和正在面临的挑战。

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