Li Changjin, Yang Fan, Yuan Zuohui, Wei Xiaoguo
Department of Gastroenterology, Gansu Provincial Hospital, Lanzhou 730000, Gansu, China.
Biomol Biomed. 2025 May 15;25(10):2151-2170. doi: 10.17305/bb.2025.12465.
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and poses a serious threat to public health. NAFLD is considered a risk factor for metabolic syndrome (MS) and is closely associated with type 2 diabetes mellitus (T2DM), obesity, dyslipidemia, and cardiovascular disease. Recently, increasing attention has been paid to the role of RNA-binding proteins (RBPs) in the pathogenesis of NAFLD. A growing body of research has linked RBPs-such as human antigen R (HuR), sequestosome 1 (p62), polypyrimidine tract-binding protein 1 (PTBP1), and heterogeneous nuclear ribonucleoproteins (hnRNPs)-to lipogenesis and inflammation, both of which contribute to NAFLD through mechanisms involving transcriptional regulation, alternative splicing, RNA stability, polyadenylation, and subcellular localization. However, these findings are often fragmented and lack a comprehensive synthesis. The interactions and mechanisms between RBPs and NAFLD have not yet been thoroughly reviewed. This article provides an overview of the roles and mechanisms of various RBPs in NAFLD, summarizing current knowledge with the aid of figures and tables. In particular, it highlights the influence of HuR on NAFLD through multiple pathways, categorizing its effects based on increased or decreased expression. Furthermore, it reviews drugs that alleviate NAFLD by modulating RBPs, aiming to offer valuable insights for drug-targeted therapies based on RBP regulatory networks.
非酒精性脂肪性肝病(NAFLD)是全球最常见的慢性肝病,对公众健康构成严重威胁。NAFLD被认为是代谢综合征(MS)的一个危险因素,并且与2型糖尿病(T2DM)、肥胖、血脂异常和心血管疾病密切相关。最近,RNA结合蛋白(RBPs)在NAFLD发病机制中的作用受到了越来越多的关注。越来越多的研究将RBPs——如人类抗原R(HuR)、聚集体蛋白1(p62)、多嘧啶序列结合蛋白1(PTBP1)和不均一核核糖核蛋白(hnRNPs)——与脂肪生成和炎症联系起来,这两者都通过涉及转录调控、可变剪接、RNA稳定性、多聚腺苷酸化和亚细胞定位的机制促成NAFLD。然而,这些发现往往是零散的,缺乏全面的综合。RBPs与NAFLD之间的相互作用和机制尚未得到全面综述。本文概述了各种RBPs在NAFLD中的作用和机制,借助图表总结了当前的知识。特别是,它强调了HuR通过多种途径对NAFLD的影响,并根据表达的增加或减少对其作用进行了分类。此外,它还综述了通过调节RBPs来缓解NAFLD的药物,旨在为基于RBP调控网络的药物靶向治疗提供有价值的见解。