Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
J Cell Physiol. 2021 Sep;236(9):6200-6224. doi: 10.1002/jcp.30311. Epub 2021 Feb 8.
Posttranscriptional regulation is a mechanism for the cells to control gene regulation at the RNA level. In this process, RNA-binding proteins (RBPs) play central roles and orchestrate the function of RNA molecules in multiple steps. Accumulating evidence has shown that the aberrant regulation of RBPs makes contributions to the initiation and progression of tumorigenesis via numerous mechanisms such as genetic changes, epigenetic alterations, and noncoding RNA-mediated regulations. In this article, we review the effects caused by RBPs and their functional diversity in the malignant transformation of cancer cells that occurs through the involvement of these proteins in various stages of RNA regulation including alternative splicing, stability, polyadenylation, localization, and translation. Besides this, we review the various interactions between RBPs and other crucial posttranscriptional regulators such as microRNAs and long noncoding RNAs in the pathogenesis of cancer. Finally, we discuss the potential approaches for targeting RBPs in human cancers.
转录后调控是细胞在 RNA 水平控制基因调控的一种机制。在这个过程中，RNA 结合蛋白 (RBP) 发挥着核心作用，并在多个步骤中协调 RNA 分子的功能。越来越多的证据表明，RBP 的异常调节通过多种机制，如遗传改变、表观遗传改变和非编码 RNA 介导的调节，为肿瘤发生的起始和进展做出了贡献。在本文中，我们综述了 RBP 及其在癌细胞恶性转化中的功能多样性所产生的影响，这些蛋白参与了 RNA 调控的各个阶段，包括可变剪接、稳定性、多聚腺苷酸化、定位和翻译。此外，我们还综述了 RBP 与其他关键转录后调节剂（如 microRNAs 和长非编码 RNA）在癌症发病机制中的各种相互作用。最后，我们讨论了在人类癌症中靶向 RBP 的潜在方法。
