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mA、mC 和 Ψ RNA 修饰在癌症中的作用:新的治疗机会。

The role of mA, mC and Ψ RNA modifications in cancer: Novel therapeutic opportunities.

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.

出版信息

Mol Cancer. 2021 Jan 18;20(1):18. doi: 10.1186/s12943-020-01263-w.

Abstract

RNA modifications have recently emerged as critical posttranscriptional regulators of gene expression programmes. Significant advances have been made in understanding the functional role of RNA modifications in regulating coding and non-coding RNA processing and function, which in turn thoroughly shape distinct gene expression programmes. They affect diverse biological processes, and the correct deposition of many of these modifications is required for normal development. Alterations of their deposition are implicated in several diseases, including cancer. In this Review, we focus on the occurrence of N-methyladenosine (mA), 5-methylcytosine (mC) and pseudouridine (Ψ) in coding and non-coding RNAs and describe their physiopathological role in cancer. We will highlight the latest insights into the mechanisms of how these posttranscriptional modifications influence tumour development, maintenance, and progression. Finally, we will summarize the latest advances on the development of small molecule inhibitors that target specific writers or erasers to rewind the epitranscriptome of a cancer cell and their therapeutic potential.

摘要

RNA 修饰最近已成为基因表达程序转录后调控的关键因素。在理解 RNA 修饰在调节编码和非编码 RNA 加工和功能方面的功能作用方面取得了重大进展,这反过来又彻底塑造了不同的基因表达程序。它们影响多种生物学过程,许多这些修饰的正确沉积对于正常发育是必需的。它们沉积的改变与包括癌症在内的几种疾病有关。在这篇综述中,我们重点关注 mA、mC 和 Ψ 在编码和非编码 RNA 中的存在,并描述它们在癌症中的生理病理作用。我们将强调最新的见解,即这些转录后修饰如何影响肿瘤的发生、维持和进展。最后,我们将总结开发针对特定写入器或擦除器的小分子抑制剂以重写癌细胞的表观转录组及其治疗潜力的最新进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fae/7812662/39893407fba8/12943_2020_1263_Fig1_HTML.jpg

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