Mancarella Caterina, Scotlandi Katia
Laboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
Front Cell Dev Biol. 2020 Jan 15;7:363. doi: 10.3389/fcell.2019.00363. eCollection 2019.
RNA network control is a key aspect of proper cellular homeostasis. In this context, RNA-binding proteins (RBPs) play a major role as regulators of the RNA life cycle due to their capability to bind to RNA sequences and precisely direct nuclear export, translation/degradation rates, and the intracellular localization of their target transcripts. Alterations in RBP expression or functions result in aberrant RNA translation and may drive the emergence and progression of several pathological conditions, including cancer. Among the RBPs, insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) is of particular interest in tumorigenesis and tumor progression. This review highlights the molecular mechanisms underlying the oncogenic functions of IGF2BP3, summarizes the therapeutic potential related to its inhibition and notes the fundamental issues that remain unanswered. To fully exploit IGF2BP3 for tumor diagnosis and therapy, it is crucial to dissect the mechanisms governing IGF2BP3 re-expression and to elucidate the complex interactions between IGF2BP3 and its target mRNAs as normal cells become tumor cells.
RNA网络调控是细胞内环境稳定的关键方面。在此背景下,RNA结合蛋白(RBPs)作为RNA生命周期的调节因子发挥着主要作用,因为它们能够与RNA序列结合,并精确指导核输出、翻译/降解速率及其靶转录本的细胞内定位。RBP表达或功能的改变会导致RNA翻译异常,并可能推动包括癌症在内的多种病理状况的发生和发展。在RBPs中,胰岛素样生长因子2 mRNA结合蛋白3(IGF2BP3)在肿瘤发生和肿瘤进展中尤为引人关注。本综述重点介绍了IGF2BP3致癌功能的分子机制,总结了与其抑制相关的治疗潜力,并指出了尚未解决的基本问题。为了充分利用IGF2BP3进行肿瘤诊断和治疗,剖析调控IGF2BP3重新表达的机制以及阐明正常细胞转变为肿瘤细胞时IGF2BP3与其靶mRNA之间的复杂相互作用至关重要。