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RNA 修饰在癌症代谢和肿瘤微环境中的作用。

RNA Modifications in Cancer Metabolism and Tumor Microenvironment.

机构信息

Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA, 91016, USA.

Department of General Surgery, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China.

出版信息

Cancer Treat Res. 2023;190:3-24. doi: 10.1007/978-3-031-45654-1_1.

Abstract

RNA modifications have recently been recognized as essential posttranscriptional regulators of gene expression in eukaryotes. Investigations over the past decade have revealed that RNA chemical modifications have profound effects on tumor initiation, progression, refractory, and recurrence. Tumor cells are notorious for their robust plasticity in response to the stressful microenvironment and undergo metabolic adaptations to sustain rapid cell proliferation, which is termed as metabolic reprogramming. Meanwhile, cancer-associated metabolic reprogramming leads to substantial alterations of intracellular and extracellular metabolites, which further reshapes the tumor microenvironment (TME). Moreover, cancer cells compete with tumor-infiltrating immune cells for the limited nutrients to maintain their proliferation and function in the TME. In this chapter, we review recent interesting findings on the engagement of epitranscriptomic pathways, especially the ones associated with N-methyladenosine (mA), in the regulation of cancer metabolism and the surrounding microenvironment. We also discuss the promising therapeutic approaches targeting RNA modifications for anti-tumor therapy.

摘要

RNA 修饰最近被认为是真核生物中基因表达的重要转录后调控因子。过去十年的研究表明,RNA 化学修饰对肿瘤的发生、进展、耐药性和复发有深远的影响。肿瘤细胞以其对应激微环境的强大可塑性而闻名,并进行代谢适应以维持快速细胞增殖,这被称为代谢重编程。同时,与癌症相关的代谢重编程导致细胞内和细胞外代谢物的大量改变,进一步重塑肿瘤微环境 (TME)。此外,癌细胞与肿瘤浸润免疫细胞争夺有限的营养物质,以维持其在 TME 中的增殖和功能。在本章中,我们综述了最近关于表观转录组途径(特别是与 N6-甲基腺苷 (m6A) 相关的途径)在调节肿瘤代谢和周围微环境中的作用的有趣发现。我们还讨论了针对 RNA 修饰的有前途的治疗方法在抗肿瘤治疗中的应用。

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