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碱基修饰和DNA修复蛋白在肿瘤微小RNA加工中的新作用:癌症生物学的新见解

Emerging roles of bases modifications and DNA repair proteins in onco-miRNA processing: novel insights in cancer biology.

作者信息

Mangiapane Giovanna, D'Agostino Vito Giuseppe, Tell Gianluca

机构信息

Laboratory of Molecular Biology and DNA repair, Department of Medicine (DMED), University of Udine, Udine, Italy.

Laboratory of Biotechnology and Nanomedicine, Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Trento, Italy.

出版信息

Cancer Gene Ther. 2024 Dec;31(12):1765-1772. doi: 10.1038/s41417-024-00836-x. Epub 2024 Sep 25.

Abstract

Onco-microRNAs (onco-miRNAs) are essential players in the post-transcriptional regulation of gene expression and exert a crucial role in tumorigenesis. Novel information about the epitranscriptomic modifications, involved in onco-miRNAs biogenesis, and in the modulation of their interplay with regulatory factors responsible for their processing and sorting are emerging. In this review, we highlight the contribution of bases modifications, sequence motifs, and secondary structures on miRNAs processing and sorting. We focus on several modes of action of RNA binding proteins (RBPs) on these processes. Moreover, we describe the new emerging scenario that shows an unexpected though essential role of selected DNA repair proteins in actively participating in these events, highlighting the original intervention represented by the non-canonical functions of Apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1), a central player in Base Excision Repair (BER) pathway of DNA lesions. Taking advantage of this new knowledge will help in prospecting new cancer diagnostic and therapeutic strategies.

摘要

肿瘤微小RNA(onco-miRNA)是基因表达转录后调控的关键参与者,在肿瘤发生过程中发挥着至关重要的作用。有关参与onco-miRNA生物发生以及调节其与负责加工和分选的调控因子相互作用的表观转录组修饰的新信息正在不断涌现。在这篇综述中,我们强调了碱基修饰、序列基序和二级结构对miRNA加工和分选的作用。我们重点关注RNA结合蛋白(RBP)在这些过程中的几种作用模式。此外,我们描述了新出现的情况,即选定的DNA修复蛋白在积极参与这些事件中发挥了意想不到但至关重要的作用,突出了无嘌呤/无嘧啶内切脱氧核糖核酸酶1(APE1)的非经典功能所代表的原始干预,APE1是DNA损伤碱基切除修复(BER)途径中的核心参与者。利用这些新知识将有助于探索新的癌症诊断和治疗策略。

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