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血液系统恶性肿瘤中的 RNA 修饰。

RNA modifications in hematological malignancies.

机构信息

Terry Fox Laboratory, British Columbia Cancer Research Centre, University of British Columbia, Vancouver, Canada.

Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.

出版信息

Int J Hematol. 2023 Jun;117(6):807-820. doi: 10.1007/s12185-023-03576-0. Epub 2023 Mar 16.

Abstract

RNA modifications play an important role in various cancers including blood cancers by controlling gene expression programs critical for survival, proliferation and differentiation of cancer cells. While hundreds of RNA modifications have been identified, many have not been functionally characterized. With development of enabling technologies to identify and map RNA modifications, tremendous advancement has been made in our understanding of the biological functions of these molecular markers in diverse cellular contexts. In the last 5 years, N-methyladenosine (mA), the most prevalent internal mRNA modification, has been extensively implicated in many facets of leukemogenesis. Other types of RNA modifications are also involved in the regulation of cell fate decisions and tumorigenesis. Here, we summarize existing knowledge and recent discoveries regarding the role of RNA modifications in leukemia. We choose to highlight cutting-edge techniques to characterize and profile RNA modifications while discussing critical functions of key modifiers and regulatory mechanisms in the pathogenesis of hematological malignancies and touch on therapeutic strategies targeting RNA modifications. These important advancements in the field will continue to foster a strong foundation for the development of innovative treatments for hematological malignancies.

摘要

RNA 修饰在包括血液癌症在内的各种癌症中起着重要作用,通过控制对癌细胞的生存、增殖和分化至关重要的基因表达程序。虽然已经鉴定了数百种 RNA 修饰,但许多修饰尚未具有功能特征。随着鉴定和绘制 RNA 修饰的使能技术的发展,我们对这些分子标记在不同细胞环境中的生物学功能的理解取得了巨大进展。在过去的 5 年中,N6-甲基腺苷(m6A),最常见的内部 mRNA 修饰,广泛参与了白血病发生的多个方面。其他类型的 RNA 修饰也参与了细胞命运决定和肿瘤发生的调控。在这里,我们总结了关于 RNA 修饰在白血病中的作用的现有知识和最新发现。我们选择强调描述和分析 RNA 修饰的前沿技术,同时讨论关键修饰因子和调节机制在血液恶性肿瘤发病机制中的关键功能,并探讨针对 RNA 修饰的治疗策略。该领域的这些重要进展将继续为血液恶性肿瘤的创新治疗方法的发展奠定坚实的基础。

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