RNA 假尿嘧啶化对癌症生物学和治疗学的影响：叙述性综述。
Implications of RNA pseudouridylation for cancer biology and therapeutics: a narrative review.
机构信息
Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Department of Hematology, Shaoxing People's Hospital, Shaoxing, Zhejiang, China.
出版信息
J Transl Med. 2024 Oct 7;22(1):906. doi: 10.1186/s12967-024-05687-6.
BACKGROUND
Pseudouridine (Ψ), a C5-glycoside isomer of uridine, stands as one of the most prevalent RNA modifications in all RNA types. Distinguishing from the C-N bond linking uridine to ribose, the link between Ψ and ribose is a C-C bond, endowing Ψ modified RNA distinct properties and functions in various biological processes. The conversion of uridine to Ψ is governed by pseudouridine synthases (PUSs). RNA pseudouridylation is implicated in cancer biology and therapeutics.
OBJECTIVES
In this review, we will summarize the methods for detecting Ψ, the process of Ψ generation, the impact of Ψ modification on RNA metabolism and gene expression, the roles of dysregulated Ψ and pseudouridine synthases in cancers, and the underlying mechanism.
METHODS
We conducted a comprehensive search of PubMed from its inception through February 2024. The search terms included "pseudouridine"; "pseudouridine synthase"; "PUS"; "dyskerin"; "cancer"; "tumor"; "carcinoma"; "malignancy"; "tumorigenesis"; "biomarker"; "prognosis" and "therapy". We included studies published in peer-reviewed journals that focused on Ψ detection, specific mechanisms involving Ψ and PUSs, and prognosis in cancer patients with high Ψ expression. We excluded studies lacking sufficient methodological details or appropriate controls.
RESULTS
Ψ has been recognized as a significant biomarker in cancer diagnosis and prognosis. Abnormal Ψ modifications mediated by various PUSs result in dysregulated RNA metabolism and impaired RNA function, promoting the development of various cancers. Overexpression of PUSs is common in cancer cells and predicts poor prognosis. PUSs inhibition arrests cell proliferation and enhances apoptosis in cancer cells, suggesting PUS-targeting cancer therapy may be a potential strategy in cancer treatment.
DISCUSSION
High Ψ levels in serum, urine, and saliva may suggest cancer, but do not specify the type, requiring additional lab markers and imaging for accurate diagnosis. Standardized detection methods are also crucial for reliable results. PUSs are linked to cancer, but more researches are needed to understand their mechanisms in different cancers. Anticancer treatments targeting PUSs are still under developed.
背景
假尿嘧啶核苷（Ψ）是尿嘧啶的 C5-糖苷异构体，是所有 RNA 类型中最普遍的 RNA 修饰之一。与连接尿嘧啶和核糖的 C-N 键不同，Ψ 与核糖之间的键是 C-C 键，这赋予了 Ψ 修饰 RNA 在各种生物过程中独特的性质和功能。尿嘧啶向 Ψ 的转化由假尿嘧啶核苷合成酶（PUS）控制。RNA 假尿嘧啶化与癌症生物学和治疗学有关。
目的
在这篇综述中，我们将总结检测 Ψ 的方法、Ψ 的生成过程、Ψ 修饰对 RNA 代谢和基因表达的影响、失调的 Ψ 和假尿嘧啶核苷合成酶在癌症中的作用以及潜在的机制。
方法
我们从创建到 2024 年 2 月在 PubMed 上进行了全面搜索。搜索词包括“假尿嘧啶”；“假尿嘧啶核苷合成酶”；“PUS”；“核仁蛋白”；“癌症”；“肿瘤”；“癌”；“恶性肿瘤”；“肿瘤发生”；“生物标志物”；“预后”和“治疗”。我们纳入了发表在同行评议期刊上的研究，这些研究重点关注 Ψ 的检测、涉及 Ψ 和 PUS 的特定机制以及高 Ψ 表达的癌症患者的预后。我们排除了缺乏足够方法学细节或适当对照的研究。
结果
Ψ 已被认为是癌症诊断和预后的重要生物标志物。各种 PUS 介导的异常 Ψ 修饰导致 RNA 代谢失调和 RNA 功能受损，促进了各种癌症的发展。PUS 的过表达在癌细胞中很常见，并预示着预后不良。PUS 抑制剂可阻止癌细胞增殖并增强癌细胞凋亡，表明针对 PUS 的癌症治疗可能是癌症治疗的一种潜在策略。
讨论
血清、尿液和唾液中的高 Ψ 水平可能提示癌症，但不能确定癌症的类型，需要额外的实验室标志物和影像学检查以进行准确诊断。标准化的检测方法对于可靠的结果也至关重要。PUS 与癌症有关，但需要更多的研究来了解它们在不同癌症中的机制。针对 PUS 的抗癌治疗仍在开发中。
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