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肿瘤中ALKBH5与读取蛋白之间的相互作用:功能与分子机制

Interactions between ALKBH5 and reader proteins in tumors: functions and molecular mechanisms.

作者信息

Ou Jiahui, Liu Bingchen, Yu Yi, He Yingchun, Gao Yuyu, Chen Lingli, Chen Xia, Tao Huai

机构信息

School of Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China.

Hunan Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China.

出版信息

Front Oncol. 2025 Sep 1;15:1611007. doi: 10.3389/fonc.2025.1611007. eCollection 2025.

DOI:10.3389/fonc.2025.1611007
PMID:40958857
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12433861/
Abstract

RNA methylation modifications are widespread in eukaryotes and prokaryotes, with N6-methyladenosine (m6A) methylation being the most prevalent internal modification in eukaryotic mRNA and having become a prominent focus of tumor research in recent years. Up to now, substantial evidence has suggested that the dysregulated RNA demethylase ALKBH5 can interact with m6A reader proteins to modulate a wide range of mRNA biological progress, including mRNA shearing, export, metabolism, and stability, ultimately influencing tumorigenesis and development. To deeply understand the regulatory roles of ALKBH5 and reader proteins in tumor progression, this review aims to summarize the structures of ALKBH5 and reader proteins, as well as their cooperative regulatory mechanisms that affect the occurrence and development of tumors originating from different systems. Furthermore, the potential applications of targeting ALKBH5 and reader proteins in antitumor drug development are summarized, hoping to provide a strong basis for advancing antineoplastic research in the future.

摘要

RNA甲基化修饰在真核生物和原核生物中广泛存在,其中N6-甲基腺苷(m6A)甲基化是真核生物mRNA中最普遍的内部修饰,并且近年来已成为肿瘤研究的一个突出焦点。到目前为止,大量证据表明,失调的RNA去甲基化酶ALKBH5可以与m6A阅读蛋白相互作用,调节广泛的mRNA生物学进程,包括mRNA剪接、输出、代谢和稳定性,最终影响肿瘤的发生和发展。为了深入了解ALKBH5和阅读蛋白在肿瘤进展中的调控作用,本综述旨在总结ALKBH5和阅读蛋白的结构,以及它们影响不同系统来源肿瘤发生和发展的协同调控机制。此外,还总结了靶向ALKBH5和阅读蛋白在抗肿瘤药物开发中的潜在应用,希望为未来推进抗肿瘤研究提供有力依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9be6/12433861/72575027ae24/fonc-15-1611007-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9be6/12433861/2050f0462346/fonc-15-1611007-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9be6/12433861/20ea5ae6481d/fonc-15-1611007-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9be6/12433861/11f141ff7525/fonc-15-1611007-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9be6/12433861/72575027ae24/fonc-15-1611007-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9be6/12433861/2050f0462346/fonc-15-1611007-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9be6/12433861/20ea5ae6481d/fonc-15-1611007-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9be6/12433861/11f141ff7525/fonc-15-1611007-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9be6/12433861/72575027ae24/fonc-15-1611007-g004.jpg

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Acta Pharm Sin B. 2025 Mar;15(3):1552-1570. doi: 10.1016/j.apsb.2024.12.037. Epub 2025 Jan 3.
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Nat Commun. 2025 May 6;16(1):4214. doi: 10.1038/s41467-025-58966-1.
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YTHDF3 drives tumor growth and metastasis by recruiting eIF4B to promote Notch2 translation in breast cancer.
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Cancer Lett. 2025 Apr 1;614:217534. doi: 10.1016/j.canlet.2025.217534. Epub 2025 Feb 7.
4
m6A-modified circXPO1 accelerates colorectal cancer progression via interaction with FMRP to promote WWC2 mRNA decay.m6A 修饰的 circXPO1 通过与 FMRP 相互作用促进 WWC2 mRNA 降解,从而加速结直肠癌的进展。
J Transl Med. 2024 Oct 14;22(1):931. doi: 10.1186/s12967-024-05716-4.
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Mol Carcinog. 2025 Jan;64(1):57-71. doi: 10.1002/mc.23826. Epub 2024 Oct 10.
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