N6甲基腺苷表转录组在非酒精性脂肪性肝病和肝细胞癌中的作用

Smart medicine Pub Date : 2023-06-02 eCollection Date: 2023-08-01 DOI:10.1002/SMMD.20230008
Yuyan Chen, Zhengyi Zhu, Lu Zhang, Jinglin Wang, Haozhen Ren
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摘要

非酒精性脂肪性肝病(NAFLD)是一种典型的慢性肝病,与发展为肝细胞癌(HCC)的高风险相关。NAFLD和HCC的发展与表观遗传学的变化有关,如组蛋白修饰和微RNA (miRNA)介导的过程。最近,在表转录组学领域,RNA的改变已经成为重要的调控因子。N6‐甲基腺苷(m6A)是控制mRNA稳定性、剪接和翻译的最常见和最关键的改变。它对控制肝脏疾病的进展和肝功能尤为重要。本文旨在总结m6A表转录组在NAFLD和HCC发生的分子机制中的作用,重点关注m6A改变对HCC发生的影响及其在NAFLD向HCC进展中的可能作用。此外,本文还讨论了m6A改变对NAFLD和HCC治疗和诊断的可能影响。重要的是要记住,m6A修饰是一种可逆的行为,通过蛋白质的写入和删除的协调功能控制,使其能够快速适应环境变化。本文还讨论了m6A结合蛋白在mRNA选择性剪接、翻译和降解中的功能,以及它们调节mRNA稳定性和加工的能力。了解RNA修饰调控及其在HCC和NAFLD发生中的作用可能为这些疾病的诊断和治疗提供新的途径。
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Roles of N6-methyladenosine epitranscriptome in non-alcoholic fatty liver disease and hepatocellular carcinoma.

Non-alcoholic fatty liver disease (NAFLD) is a typical chronic liver disease connected to a high risk of developing hepatocellular carcinoma (HCC). The development of NAFLD and HCC has been associated with changes in epigenetics, such as histone modifications and micro RNA (miRNA)-mediated processes. Recently, in the realm of epitranscriptomics, RNA alterations have become important regulators. N6-methyladenosine (m6A) is the most common and crucial alteration for controlling mRNA stability, splicing, and translation. It is particularly important for controlling liver disease progression and hepatic function. This review aims to conclude recent research on the functions of m6A epitranscriptome in the molecular mechanisms behind NAFLD and HCC development, with special attention to the effects of m6A alteration on how HCC develops and its possible roles in the progression of NAFLD to HCC. Additionally, the review discusses the possible effects of m6A alteration on the treatment and diagnostic of NAFLD and HCC. It is crucial to remember that m6A modification is a reversible action controlled via the coordinated functions of the proteins that write and delete, enabling quick adaptability to environmental changes. The review also discusses m6A-binding proteins' function in mRNA alternative splicing, translation, and degradation and their ability to modulate mRNA stability and processing. Understanding RNA modification regulation and its part in the emergence of HCC and NAFLD may provide new avenues for diagnosing and treating these diseases.

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