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RNA结合蛋白介导的癌症竞争性内源性RNA机制

RNA binding protein-mediated competing endogenous RNA mechanism in cancer.

作者信息

Zhu Jingyu, Mo Yin-Yuan, Peng Wan-Xin

机构信息

Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medicine University (Hangzhou Hospital of Traditional Chinese Medicine), Hangzhou, China.

Institute of Clinical Medicine, Zhejiang Provincial People's Hospital, Hangzhou, China.

出版信息

Gene. 2025 Sep 5;963:149606. doi: 10.1016/j.gene.2025.149606. Epub 2025 Jun 4.

Abstract

It is evidently now that long non-coding RNAs (lncRNAs) play vital roles in development of cancer through versatile mechanisms. Of importance, lncRNAs play such a regulatory role often through interacting with their partners, including DNAs, RNAs or proteins. Thus, it is critical to dissect the interaction of lncRNAs with their binding partners in order to fully understand the mechanism underlying the lncRNA-mediated gene expression. In this review, we present the current state of knowledge implicating lncRNAs in gene regulation through RNA binding proteins (RBPs). We first describe briefly the known functions of lncRNAs and then introduce RBPs related to lncRNA function. We also touch on DNA-RNA binding proteins (DRBPs) as a special group of RBPs and how lncRNAs interact with DRBPs, leading to gene expression. Next, we provide a few examples such as RBP-mediated RNA stability, alternative splicing and RNA methylation to highlight the importance of lncRNA-RBP interaction. Finally, we compare RPBs with microRNAs for their functions in gene regulation. It is well known that microRNAs can silence multiple targets including coding genes and non-coding genes through microRNA response elements (MREs); similarly, RBPs can regulate targeted genes through RBP binding sites (RBP-BSs). However, RBPs often carry multiple RNA binding domains and they are also capable of interacting with other proteins or RNAs, forming a "competing endogenous RNA (ceRNA)" network. With involvement of lncRNAs, this regulatory system becomes even more complex and powerful. Thus, the detailed dissection of the lncRNA-RBP interaction will provide new insight into this gene regulatory system.

摘要

显然,长链非编码RNA(lncRNA)如今通过多种机制在癌症发展中发挥着至关重要的作用。重要的是,lncRNA通常通过与包括DNA、RNA或蛋白质在内的伙伴相互作用来发挥这种调节作用。因此,剖析lncRNA与其结合伙伴之间的相互作用对于全面理解lncRNA介导的基因表达机制至关重要。在本综述中,我们介绍了当前关于lncRNA通过RNA结合蛋白(RBP)参与基因调控的知识现状。我们首先简要描述lncRNA的已知功能,然后介绍与lncRNA功能相关的RBP。我们还涉及作为RBP特殊群体的DNA-RNA结合蛋白(DRBP)以及lncRNA如何与DRBP相互作用从而导致基因表达。接下来,我们提供一些例子,如RBP介导的RNA稳定性、可变剪接和RNA甲基化,以突出lncRNA-RBP相互作用的重要性。最后,我们比较RBP与微小RNA在基因调控中的功能。众所周知,可以通过微小RNA反应元件(MRE)使包括编码基因和非编码基因在内的多个靶标沉默;同样,RBP可以通过RBP结合位点(RBP-BS)调节靶基因。然而,RBP通常携带多个RNA结合结构域,它们还能够与其他蛋白质或RNA相互作用,形成一个“竞争性内源RNA(ceRNA)”网络。在lncRNA的参与下,这个调控系统变得更加复杂和强大。因此,对lncRNA-RBP相互作用的详细剖析将为这个基因调控系统提供新的见解。

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