碱基修饰与DNA修复蛋白在肿瘤miRNA加工中的新兴作用: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
原文发布日期:2024-09-25
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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.
癌源微小核糖核酸(onco-miRNAs)在基因表达的转录后调控中扮演关键角色,并对肿瘤发生具有重要影响。关于表观转录组修饰的新发现正不断涌现,这些修饰涉及癌源miRNAs的生物合成过程,并参与调控其与负责加工和分选的调控因子之间的相互作用。本综述重点探讨碱基修饰、序列基序和二级结构对miRNAs加工与分选的影响,聚焦RNA结合蛋白(RBPs)在这些过程中多种作用模式。此外,我们阐述了新兴研究揭示的突破性发现:特定DNA修复蛋白通过非常规功能积极参与这些过程,其中无嘌呤/无嘧啶内切核酸酶1(APE1)——碱基切除修复(BER)通路的核心蛋白——所表现出的非经典功能代表了原始干预机制。利用这些新认知将有助于开拓癌症诊断与治疗的新策略。
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