Non-coding RNAs, guardians of the p53 galaxy
Non-coding RNAs, guardians of the p53 galaxy
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非编码 RNA，p53 星系的守护者。
DOI：
10.1016/j.semcancer.2020.09.002
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发表时间：
2021-11-22
影响因子：
14.5
通讯作者：
Liu, Lianxin
中科院分区：
文献类型：
--
作者：
Chen, Song;Thorne, Rick F.;Liu, Lianxin
TP53基因可以说是已知的最重要的肿瘤抑制基因，在肿瘤发展过程中发挥多方面的作用。其蛋白产物p53是一种重要的序列特异性转录因子，调节蛋白质编码基因的大网络以及数千种非编码RNA（ncRNA），特别是microRNA和长ncRNA（lncRNA）的表达。通过各种直接和间接机制，ncRNA反过来调节p53水平和活性。在这里，将失调的ncRNA通过参与整个p53调控网络与肿瘤发生联系起来的研究数量正在稳步增加。本文将探讨ncRNA的主要形式，即microRNA、lncRNA和circular RNA（circRNA）在p53的多种细胞反应中是如何作为效应子或调节子发挥作用的。我们首先讨论了最近发现的miRNAs和p53信号之间的联系，然后重点关注lncRNA和p53之间明显的串扰的显着多样性，随后，开发报告将circRNA与p53联系起来。在整个审查强调的是机制的影响失调的ncRNAs对p53功能，以及这些相互作用可能的预后影响。我们还描述了ncRNA和突变型p53的经常令人困惑的功能之间的新兴联系。最后，在p53治疗方法的背景下，我们描述了ncRNA研究中的一些挑战及其翻译潜力。
The TP53 gene is arguably the most important tumor suppressor gene known, contributing multifaceted roles to the process of tumor development. Its protein product p53, is a crucial sequence-specific transcription factor which regulates the expression of a large network of protein-coding genes, as well as thousands of noncoding RNAs (ncRNAs), notably microRNAs and long ncRNAs (lncRNAs). Through a variety of direct and indirect mechanisms, ncRNAs in turn modulate p53 levels and activity. Here the numbers of studies are steadily building which link the contributions of dysregulated ncRNAs to tumorigenesis via their participation throughout the p53 regulatory network. In this review, we will examine how the principal forms of ncRNAs, namely microRNAs, lncRNAs and circular RNAs (circRNAs) function as either effectors or regulators amongst the diversity of p53 ' s cellular responses. We first discuss the more recently discovered connections between miRNAs and p53 signaling before focusing on the remarkable diversity of crosstalk evident between lncRNAs and p53, and subsequently, developing reports linking circRNAs to p53. Highlighted throughout the review are the mechanistic impacts of dysregulated ncRNAs on p53 functions as well as the possible prognostic implications of these interactions. We also describe the emerging connections between ncRNAs and the often-perplexing functions of mutant p53. Finally, in the context of p53 therapeutic approaches, we describe some of the challenges in ncRNA research and their potential for translation.