Sobolewski Cyril, Dubuquoy Laurent, Legrand Noémie
Inserm, CHU Lille, U1286-INFINITE-Institute for Translational Research in Inflammation, Univ. Lille, F-59000 Lille, France.
Cancers (Basel). 2022 Jul 20;14(14):3516. doi: 10.3390/cancers14143516.
MicroRNAs represent the most characterized post-transcriptional regulators of gene expression. Their altered expression importantly contributes to the development of a wide range of metabolic and inflammatory diseases but also cancers. Accordingly, a myriad of studies has suggested novel therapeutic approaches aiming at inhibiting or restoring the expression of miRNAs in human diseases. However, the influence of other trans-acting factors, such as long-noncoding RNAs or RNA-Binding-Proteins, which compete, interfere, or cooperate with miRNAs-dependent functions, indicate that this regulatory mechanism is much more complex than initially thought, thus questioning the current models considering individuals regulators. In this review, we discuss the interplay existing between miRNAs and the AU-Rich Element Binding Proteins (AUBPs), HuR and tristetraprolin family members (TTP, BRF1 and BRF2), which importantly control the fate of mRNA and whose alterations have also been associated with the development of a wide range of chronic disorders and cancers. Deciphering the interplay between these proteins and miRNAs represents an important challenge to fully characterize the post-transcriptional regulation of pro-tumorigenic processes and design new and efficient therapeutic approaches.
微小RNA是基因表达中最具特征的转录后调节因子。它们表达的改变不仅对多种代谢性疾病、炎症性疾病的发展起着重要作用,也与癌症的发生密切相关。因此,大量研究提出了针对抑制或恢复人类疾病中微小RNA表达的新型治疗方法。然而,其他反式作用因子,如长链非编码RNA或RNA结合蛋白,它们与微小RNA依赖性功能存在竞争、干扰或协同作用,这表明这种调节机制比最初认为的要复杂得多,从而对当前考虑单个调节因子的模型提出了质疑。在这篇综述中,我们讨论了微小RNA与富含AU元件结合蛋白(AUBP)、HuR以及锌指蛋白家族成员(TTP、BRF1和BRF2)之间存在的相互作用,这些蛋白对信使核糖核酸的命运起着重要调控作用,其改变也与多种慢性疾病和癌症的发生有关。解析这些蛋白与微小RNA之间的相互作用是全面阐明促肿瘤过程转录后调控机制以及设计新型高效治疗方法的一项重要挑战。