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癌症中的DDX27:分子机制、临床意义及治疗潜力

DDX27 in cancer: molecular mechanisms, clinical implications, and therapeutic potential.

作者信息

Yang Le, Mok Simon Wing-Fai, Li Hua Hui, Wong Io Nam, Yang Li Jun

机构信息

Department of Gastroenterology, Yi Yang Central Hospital, Yiyang, China.

Faculty of Medicine, Macau University of Science and Technology, Taipa, 999078, Macau, China.

出版信息

J Transl Med. 2025 Aug 28;23(1):971. doi: 10.1186/s12967-025-07004-1.

DOI:10.1186/s12967-025-07004-1
PMID:40877927
Abstract

BACKGROUND

DDX27, a member of the DEAD-box RNA helicase family, plays a pivotal role in RNA metabolism and is essential for diverse cellular processes, including transcription, pre-mRNA splicing, translation, and ribosome biogenesis. Recent findings have implicated DDX27 as a substantial contributor to tumorigenesis and cancer progression across various malignancies, establishing its significance as a molecular hub that interacts with key oncogenic partners such as major vault protein (MVP) and nucleophosmin 1 (NPM1).

METHODS

We conducted systematic search in the following comprehensive academic databases: PubMed, MEDLINE or Web of Science. The keywords such as DDX27, DEAD-box protein 27, RNA helicase DDX27 and cancer, tumor or carcinoma were used for searching. This review consolidates the existing literature on DDX27, examining its structural features and biological functions within the context of tumorigenesis. We systematically explore the molecular mechanisms by which DDX27 influences tumor development and progression, focusing particularly on its roles across different cancer types, including colorectal cancer (CRC), gastric cancer (GC), breast cancer (BC), hepatocellular carcinoma (HCC), and oral squamous cell carcinoma (OSCC). Key molecular mechanisms such as NF-κB activation and ERK1/2 phosphorylation involved in DDX27-related pathways are discussed.

RESULTS

Our comprehensive summary elucidates the context-dependent roles of DDX27 across various cancers, highlighting its associations with advanced disease stages, metastasis, and therapeutic resistance. We also assess the potential of DDX27 as a diagnostic and prognostic biomarker, correlating its expression levels with negative clinical outcomes.

CONCLUSION

Novel therapeutic strategies targeting DDX27 are proposed, including RNA interference techniques (siRNA and shRNA), miRNA-based therapies (miR-617 mimics), pathway modulation, and synthetic lethality approaches. Furthermore, we identify notable limitations in current research surrounding DDX27 and offer potential avenues for future investigation. These innovative strategies present significant promise for the development of precision cancer therapies aimed at improving treatment outcomes for patients.

摘要

背景

DDX27是DEAD盒RNA解旋酶家族的成员,在RNA代谢中起关键作用,对多种细胞过程至关重要,包括转录、前体mRNA剪接、翻译和核糖体生物合成。最近的研究发现表明,DDX27是多种恶性肿瘤发生和癌症进展的重要促成因素,确立了其作为与主要穹窿蛋白(MVP)和核磷蛋白1(NPM1)等关键致癌伙伴相互作用的分子枢纽的重要性。

方法

我们在以下综合学术数据库中进行了系统检索:PubMed、MEDLINE或科学网。使用DDX27、DEAD盒蛋白27、RNA解旋酶DDX27以及癌症、肿瘤或癌等关键词进行检索。本综述整合了关于DDX27的现有文献,在肿瘤发生的背景下研究其结构特征和生物学功能。我们系统地探讨了DDX27影响肿瘤发展和进展的分子机制,特别关注其在不同癌症类型中的作用,包括结直肠癌(CRC)、胃癌(GC)、乳腺癌(BC)、肝细胞癌(HCC)和口腔鳞状细胞癌(OSCC)。讨论了DDX27相关途径中涉及的关键分子机制,如NF-κB激活和ERK1/2磷酸化。

结果

我们的全面总结阐明了DDX27在各种癌症中的背景依赖性作用,突出了其与晚期疾病阶段、转移和治疗耐药性的关联。我们还评估了DDX27作为诊断和预后生物标志物的潜力,将其表达水平与不良临床结果相关联。

结论

提出了针对DDX27的新型治疗策略,包括RNA干扰技术(siRNA和shRNA)、基于miRNA的疗法(miR-617模拟物)、途径调节和合成致死方法。此外,我们确定了当前围绕DDX27研究的显著局限性,并提供了未来研究的潜在途径。这些创新策略为开发旨在改善患者治疗结果的精准癌症疗法带来了巨大希望。

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本文引用的文献

1
DDX27: An RNA helicase regulating cancer progression and therapeutic prospects.DDX27:一种调节癌症进展和治疗前景的RNA解旋酶
Int J Biol Macromol. 2025 Jun;313:144388. doi: 10.1016/j.ijbiomac.2025.144388. Epub 2025 May 19.
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AI-directed formulation strategy design initiates rational drug development.人工智能导向的制剂策略设计开启了合理的药物研发。
J Control Release. 2025 Feb 10;378:619-636. doi: 10.1016/j.jconrel.2024.12.043. Epub 2024 Dec 26.
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DEAD-box helicase family proteins: emerging targets in digestive system cancers and advances in targeted drug development.
DEAD盒解旋酶家族蛋白:消化系统癌症中的新兴靶点及靶向药物开发进展
J Transl Med. 2024 Dec 20;22(1):1120. doi: 10.1186/s12967-024-05930-0.
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Deep generative AI models analyzing circulating orphan non-coding RNAs enable detection of early-stage lung cancer.深度生成式 AI 模型分析循环孤儿非编码 RNA 可实现早期肺癌检测。
Nat Commun. 2024 Nov 21;15(1):10090. doi: 10.1038/s41467-024-53851-9.
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DEAD-box RNA helicases in the multistep process of tumor metastasis.DEAD-box RNA helicases 在肿瘤转移的多步骤过程中。
Mol Biol Rep. 2024 Sep 22;51(1):1006. doi: 10.1007/s11033-024-09912-9.
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miR-617 interacts with the promoter of and positively regulates its expression: implications for cancer therapeutics.miR-617与[具体基因名称]的启动子相互作用并正向调控其表达:对癌症治疗的意义。 (你提供的原文中“the promoter of ”这里缺少具体基因名称)
Front Oncol. 2024 Jun 13;14:1411539. doi: 10.3389/fonc.2024.1411539. eCollection 2024.
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Building consensus on the application of organoid-based drug sensitivity testing in cancer precision medicine and drug development.就类器官为基础的药物敏感性测试在癌症精准医疗和药物研发中的应用达成共识。
Theranostics. 2024 May 27;14(8):3300-3316. doi: 10.7150/thno.96027. eCollection 2024.
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The Story of RNA Unfolded: The Molecular Function of DEAD- and DExH-Box ATPases and Their Complex Relationship with Membraneless Organelles.RNA 解链的故事:DEAD- 和 DExH-Box ATP 酶的分子功能及其与无膜细胞器的复杂关系。
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