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RNA剪接:从治疗角度看肺部疾病中的新星。

RNA splicing: Novel star in pulmonary diseases with a treatment perspective.

作者信息

Niu Zhihui, Xu Bingqian, Li Wei, Sun Jian, Liang Haihai

机构信息

State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Pharmacology (State Key Labratoray-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, China.

Translational Medicine Research Center, Medical Pathology Center, Chongqing University Three Gorges Hospital, School of Medicine Chongqing University, Chongqing University, Chongqing 404000, China.

出版信息

Acta Pharm Sin B. 2025 May;15(5):2301-2322. doi: 10.1016/j.apsb.2025.03.023. Epub 2025 Mar 13.

Abstract

Alternative splicing (AS) serves as a fundamental regulatory mechanism in gene expression, contributing to proteomic diversity by generating an array of mRNA isoforms from precursor mRNA distinct splice site combinations. In light of the limited therapeutic options currently available, the exploration of AS as a target for drug development is of paramount importance. This review offers an exhaustive analysis of the biological functions and underlying molecular mechanisms associated with various AS-induced splice variants, RNA-binding proteins, and -elements, highlighting their significance as clinical biomarkers. We place particular emphasis on the current therapeutic applications of AS in an array of lung diseases, including but not limited to lung cancer, cystic fibrosis, silicosis, acute respiratory distress syndrome, pneumonia, asthma, chronic obstructive pulmonary diseases, pulmonary arterial hypertension, and idiopathic pulmonary fibrosis. The review delves into the role of AS events in the diagnosis and treatment of lung diseases, focusing on the regulatory influence of splicing factors and RNA-binding proteins, while also enumerating the mutated components implicated in AS misregulation. Consequently, a comprehensive understanding of the intricate mechanisms governing these splicing events could potentially offer novel avenues for the development of splicing-targeted therapeutics and diagnostic tools for the prevention and treatment of lung diseases.

摘要

可变剪接(Alternative splicing,AS)是基因表达中的一种基本调控机制,通过从前体mRNA的不同剪接位点组合产生一系列mRNA异构体,从而增加蛋白质组的多样性。鉴于目前可用的治疗选择有限,将可变剪接作为药物开发的靶点进行探索至关重要。本综述对与各种可变剪接诱导的剪接变体、RNA结合蛋白和元件相关的生物学功能及潜在分子机制进行了详尽分析,强调了它们作为临床生物标志物的重要性。我们特别关注可变剪接在一系列肺部疾病中的当前治疗应用,包括但不限于肺癌、囊性纤维化、矽肺、急性呼吸窘迫综合征、肺炎、哮喘、慢性阻塞性肺疾病、肺动脉高压和特发性肺纤维化。该综述深入探讨了可变剪接事件在肺部疾病诊断和治疗中的作用,重点关注剪接因子和RNA结合蛋白的调控影响,同时还列举了与可变剪接失调相关的突变成分。因此,全面了解这些剪接事件的复杂机制可能为开发针对剪接的治疗方法和诊断工具以预防和治疗肺部疾病提供新途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b35/12145001/de8b278eb631/ga1.jpg

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