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抗砷蛋白2与微小RNA生物合成:在癌症发展中的生物学意义

Arsenic resistance protein 2 and microRNA biogenesis: Biological implications in cancer development.

作者信息

Yuan Liang, Jiang Xiuxing, Gong Qihai, Gao Ning

机构信息

Key Laboratory of Basic Pharmacology of Ministry of Education, Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou 563006, China.

College of Pharmacy, Army Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, China.

出版信息

Pharmacol Ther. 2023 Apr;244:108386. doi: 10.1016/j.pharmthera.2023.108386. Epub 2023 Mar 16.

DOI:10.1016/j.pharmthera.2023.108386
PMID:36933704
Abstract

Arsenic resistance protein 2 (Ars2) is a nuclear protein that plays a critical role in the regulation of microRNA (miRNA) biogenesis. Ars2 is required for cell proliferation and for the early stages of mammalian development through a possible effect on miRNA processing. Increasing evidence reveal that Ars2 is highly expressed in proliferating cancer cells, suggesting that Ars2 may be a potential therapeutic target for cancer. Therefore, development of the novel Ars2 inhibitors could represent the novel therapeutic strategies for treatment of cancer. In this review, we briefly discuss the mechanisms by which Ars2 regulates miRNA biogenesis and its impact on cell proliferation and cancer development. Particularly, we mainly discuss the role of Ars2 in the regulation of cancer development and highlight pharmacological targeting of Ars2 as a promising cancer therapeutic strategy.

摘要

抗砷蛋白2(Ars2)是一种核蛋白,在微小RNA(miRNA)生物合成的调控中起关键作用。Ars2通过对miRNA加工的可能影响,对细胞增殖和哺乳动物发育的早期阶段是必需的。越来越多的证据表明,Ars2在增殖的癌细胞中高表达,这表明Ars2可能是癌症的一个潜在治疗靶点。因此,开发新型Ars2抑制剂可能代表治疗癌症的新型治疗策略。在这篇综述中,我们简要讨论了Ars2调节miRNA生物合成的机制及其对细胞增殖和癌症发展的影响。特别地,我们主要讨论了Ars2在癌症发展调控中的作用,并强调将Ars2作为一种有前景的癌症治疗策略进行药物靶向治疗。

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Arsenic resistance protein 2 and microRNA biogenesis: Biological implications in cancer development.抗砷蛋白2与微小RNA生物合成:在癌症发展中的生物学意义
Pharmacol Ther. 2023 Apr;244:108386. doi: 10.1016/j.pharmthera.2023.108386. Epub 2023 Mar 16.
2
Ars2 links the nuclear cap-binding complex to RNA interference and cell proliferation.ARS2将核帽结合复合体与RNA干扰及细胞增殖联系起来。
Cell. 2009 Jul 23;138(2):328-39. doi: 10.1016/j.cell.2009.04.046.
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Ars2 promotes cell proliferation and tumorigenicity in glioblastoma through regulating miR-6798-3p.Ars2 通过调控 miR-6798-3p 促进胶质母细胞瘤的细胞增殖和致瘤性。
Sci Rep. 2018 Oct 22;8(1):15602. doi: 10.1038/s41598-018-33905-x.
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Depletion of Ars2 inhibits cell proliferation and leukemogenesis in acute myeloid leukemia by modulating the miR-6734-3p/p27 axis.Ars2 耗竭通过调节 miR-6734-3p/p27 轴抑制急性髓系白血病细胞增殖和白血病发生。
Leukemia. 2019 May;33(5):1090-1101. doi: 10.1038/s41375-018-0301-z. Epub 2018 Dec 5.
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Mutagenesis of ARS2 Domains To Assess Possible Roles in Cell Cycle Progression and MicroRNA and Replication-Dependent Histone mRNA Biogenesis.对ARS2结构域进行诱变以评估其在细胞周期进程、微小RNA及复制依赖性组蛋白mRNA生物合成中的可能作用。
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Ars2 promotes proper replication-dependent histone mRNA 3' end formation.Ars2 促进依赖复制的组蛋白 mRNA 3' 末端形成。
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Ars2 is overexpressed in human cholangiocarcinomas and its depletion increases PTEN and PDCD4 by decreasing microRNA-21.Ars2 在人类胆管癌中过表达,其通过降低 microRNA-21 来增加 PTEN 和 PDCD4 的表达。
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miRNA biogenesis: biological impact in the development of cancer.微小RNA生物合成:在癌症发展中的生物学影响
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ARS2 Regulates Nuclear Paraspeckle Formation through 3'-End Processing and Stability of NEAT1 Long Noncoding RNA.ARS2 通过 3'-端加工和 NEAT1 长非编码 RNA 的稳定性调节核 paraspeckle 的形成。
Mol Cell Biol. 2020 Jan 30;40(4). doi: 10.1128/MCB.00269-19.

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