Department of Radiation Oncology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73013, USA; Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73013, USA.
Department of Pathology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73013, USA; Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73013, USA.
Adv Drug Deliv Rev. 2022 Dec;191:114569. doi: 10.1016/j.addr.2022.114569. Epub 2022 Oct 14.
Traditionally majority of eukaryotic gene expression is influenced by transcriptional and post-transcriptional events. Alterations in the expression of proteins that act post-transcriptionally can affect cellular signaling and homeostasis. RNA binding proteins (RBPs) are a family of proteins that specifically bind to RNAs and are involved in post-transcriptional regulation of gene expression and important cellular processes such as cell differentiation and metabolism. Deregulation of RNA-RBP interactions and any changes in RBP expression or function can lead to various diseases including cancer. In cancer cells, RBPs play an important role in regulating the expression of tumor suppressors and oncoproteins involved in various cell-signaling pathways. Several RBPs such as HuR, AUF1, RBM38, LIN28, RBM24, tristetrapolin family and Musashi play critical roles in various types of cancers and their aberrant expression in cancer cells makes them an attractive therapeutic target for cancer treatment. In this review we provide an overview of i). RBPs involved in cancer progression and their mechanism of action ii). the role of RBPs, including HuR, in breast cancer progression and DNA damage response and iii). explore RBPs with emphasis on HuR as therapeutic target for breast cancer therapy.
传统上,大多数真核基因表达受转录和转录后事件的影响。参与转录后调控的蛋白质表达的改变会影响细胞信号转导和内稳态。RNA 结合蛋白(RBPs)是一类特异性结合 RNA 的蛋白质,参与基因表达的转录后调控以及细胞分化和代谢等重要细胞过程。RNA-RBP 相互作用的失调以及 RBP 表达或功能的任何变化都可能导致各种疾病,包括癌症。在癌细胞中,RBPs 在调节肿瘤抑制因子和参与各种细胞信号通路的癌蛋白的表达中发挥重要作用。几种 RBPs,如 HuR、AUF1、RBM38、LIN28、RBM24、tristetrapolin 家族和 Musashi,在各种类型的癌症中发挥关键作用,它们在癌细胞中的异常表达使它们成为癌症治疗的有吸引力的治疗靶点。在这篇综述中,我们概述了:i)参与癌症进展的 RBPs 及其作用机制;ii)RBPs,包括 HuR,在乳腺癌进展和 DNA 损伤反应中的作用;iii)强调 HuR 作为乳腺癌治疗的治疗靶点的 RBPs。