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富含 AU 的元件结合蛋白对肝脏炎症和癌症中 mRNA 的转录后调控。

mRNA Post-Transcriptional Regulation by AU-Rich Element-Binding Proteins in Liver Inflammation and Cancer.

机构信息

Department of Cell Physiology and Metabolism and Translational Research Center in Oncohaematology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.

出版信息

Int J Mol Sci. 2020 Sep 11;21(18):6648. doi: 10.3390/ijms21186648.

Abstract

AU-rich element-binding proteins (AUBPs) represent important post-transcriptional regulators of gene expression. AUBPs can bind to the AU-rich elements present in the 3'-UTR of more than 8% of all mRNAs and are thereby able to control the stability and/or translation of numerous target mRNAs. The regulation of the stability and the translation of mRNA transcripts by AUBPs are highly complex processes that occur through multiple mechanisms depending on the cell type and the cellular context. While AUBPs have been shown to be involved in inflammatory processes and the development of various cancers, their important role and function in the development of chronic metabolic and inflammatory fatty liver diseases (FLDs), as well as in the progression of these disorders toward cancers such as hepatocellular carcinoma (HCC), has recently started to emerge. Alterations of either the expression or activity of AUBPs are indeed significantly associated with FLDs and HCC, and accumulating evidence indicates that several AUBPs are deeply involved in a significant number of cellular processes governing hepatic metabolic disorders, inflammation, fibrosis, and carcinogenesis. Herein, we discuss our current knowledge of the roles and functions of AUBPs in liver diseases and cancer. The relevance of AUBPs as potential biomarkers for different stages of FLD and HCC, or as therapeutic targets for these diseases, are also highlighted.

摘要

富含 AU 的元素结合蛋白(AUBP)是基因表达的重要转录后调控因子。AUBP 可以与超过 8%的所有 mRNA 的 3'-UTR 中存在的 AU 富含元件结合,从而能够控制许多靶 mRNA 的稳定性和/或翻译。AUBP 对 mRNA 转录物稳定性和翻译的调节是高度复杂的过程,这些过程通过多种机制发生,具体取决于细胞类型和细胞环境。虽然已经证明 AUBP 参与了炎症过程和各种癌症的发展,但它们在慢性代谢和炎症性脂肪肝疾病(FLD)的发展以及这些疾病向肝癌(HCC)等癌症的进展中的重要作用和功能最近才开始显现。AUBP 的表达或活性的改变确实与 FLD 和 HCC 显著相关,越来越多的证据表明,几种 AUBP 深度参与了许多控制肝脏代谢紊乱、炎症、纤维化和癌变的细胞过程。本文讨论了我们目前对 AUBP 在肝脏疾病和癌症中的作用和功能的认识。还强调了 AUBP 作为不同阶段 FLD 和 HCC 的潜在生物标志物或这些疾病的治疗靶点的相关性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cea/7554771/79737a5e3f22/ijms-21-06648-g001.jpg

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