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双功能蛋白MEX3A的致癌潜力

Oncogenic Potential of the Dual-Function Protein MEX3A.

作者信息

Lederer Marcell, Müller Simon, Glaß Markus, Bley Nadine, Ihling Christian, Sinz Andrea, Hüttelmaier Stefan

机构信息

Charles Tanford Protein Center, Faculty of Medicine, Institute of Molecular Medicine, Section for Molecular Cell Biology, Martin Luther University Halle-Wittenberg, Kurt-Mothes-Str. 3a, 06120 Halle, Germany.

Center for Structural Mass Spectrometry, Department of Pharmaceutical Chemistry & Bioanalytics, Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Kurt-Mothes-Str. 3, 06120 Halle (Saale), Germany.

出版信息

Biology (Basel). 2021 May 7;10(5):415. doi: 10.3390/biology10050415.

DOI:10.3390/biology10050415
PMID:34067172
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8151450/
Abstract

MEX3A belongs to the MEX3 (Muscle EXcess) protein family consisting of four members (MEX3A-D) in humans. Characteristic for MEX3 proteins is their domain structure with 2 HNRNPK homology (KH) domains mediating RNA binding and a C-terminal really interesting new gene (RING) domain that harbors E3 ligase function. In agreement with their domain composition, MEX3 proteins were reported to modulate both RNA fate and protein ubiquitination. MEX3 paralogs exhibit an oncofetal expression pattern, they are severely downregulated postnatally, and re-expression is observed in various malignancies. Enforced expression of MEX3 proteins in various cancers correlates with poor prognosis, emphasizing their oncogenic potential. The latter is supported by MEX3A's impact on proliferation, self-renewal as well as migration of tumor cells in vitro and tumor growth in xenograft studies.

摘要

MEX3A属于MEX3(肌肉过量)蛋白家族,该家族在人类中有四个成员(MEX3A - D)。MEX3蛋白的特征在于其结构域结构,具有2个介导RNA结合的HNRNPK同源(KH)结构域和一个具有E3连接酶功能的C末端真核生物中非常有趣的新基因(RING)结构域。与它们的结构域组成一致,据报道MEX3蛋白可调节RNA命运和蛋白质泛素化。MEX3旁系同源物表现出癌胚表达模式,它们在出生后严重下调,并且在各种恶性肿瘤中观察到重新表达。在各种癌症中强制表达MEX3蛋白与预后不良相关,强调了它们的致癌潜力。后者得到了MEX3A对体外肿瘤细胞增殖、自我更新以及迁移以及异种移植研究中肿瘤生长的影响的支持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96f0/8151450/629bd604fdde/biology-10-00415-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96f0/8151450/077bdee4b20d/biology-10-00415-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96f0/8151450/629bd604fdde/biology-10-00415-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96f0/8151450/077bdee4b20d/biology-10-00415-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96f0/8151450/629bd604fdde/biology-10-00415-g002.jpg

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本文引用的文献

1
Inhibition of RNA-binding proteins with small molecules.用小分子抑制RNA结合蛋白。
Nat Rev Chem. 2020 Sep;4(9):441-458. doi: 10.1038/s41570-020-0201-4. Epub 2020 Jul 15.
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MEX3A promotes development and progression of breast cancer through regulation of PIK3CA.MEX3A 通过调节 PIK3CA 促进乳腺癌的发展和进展。
Exp Cell Res. 2021 Jul 1;404(1):112580. doi: 10.1016/j.yexcr.2021.112580. Epub 2021 Apr 1.
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Understanding disorder-to-order transitions in protein-RNA complexes using molecular dynamics simulations.利用分子动力学模拟理解蛋白质-RNA 复合物中的无序到有序转变。
Mex3a启动子低甲基化可用于诊断乙肝病毒相关肝细胞癌:一项随机对照试验。
Front Pharmacol. 2024 Nov 5;15:1325869. doi: 10.3389/fphar.2024.1325869. eCollection 2024.
4
Nucleic acid-binding KH domain proteins influence a spectrum of biological pathways including as part of membrane-localized complexes.核酸结合KH结构域蛋白影响一系列生物途径,包括作为膜定位复合物的一部分。
J Struct Biol X. 2024 Jun 27;10:100106. doi: 10.1016/j.yjsbx.2024.100106. eCollection 2024 Dec.
5
MEX3A promotes colorectal cancer migration, invasion and EMT via regulating the Wnt/β-catenin signaling pathway.MEX3A 通过调控 Wnt/β-catenin 信号通路促进结直肠癌迁移、侵袭和 EMT。
J Cancer Res Clin Oncol. 2024 Jun 25;150(6):319. doi: 10.1007/s00432-024-05845-9.
6
Systematic analysis of RNA-binding proteins identifies targetable therapeutic vulnerabilities in osteosarcoma.系统分析 RNA 结合蛋白鉴定骨肉瘤靶向治疗的潜在弱点。
Nat Commun. 2024 Apr 1;15(1):2810. doi: 10.1038/s41467-024-47031-y.
7
Ubiquitylation of RUNX3 by RNA-binding ubiquitin ligase MEX3C promotes tumorigenesis in lung adenocarcinoma.RNA 结合泛素连接酶 MEX3C 对 RUNX3 的泛素化促进肺腺癌的肿瘤发生。
J Transl Med. 2024 Feb 29;22(1):216. doi: 10.1186/s12967-023-04700-8.
8
Establishment and Validation of a Four-stress Granule-related Gene Signature in Hepatocellular Carcinoma.肝细胞癌中四味抗纤颗粒相关基因特征的建立与验证
J Clin Transl Hepatol. 2024 Jan 28;12(1):1-14. doi: 10.14218/JCTH.2023.00019. Epub 2023 Jul 25.
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MEX3A determines in vivo hepatocellular carcinoma progression and induces resistance to sorafenib in a Hippo-dependent way.MEX3A 通过 Hippo 依赖性途径决定体内肝细胞癌的进展并诱导对索拉非尼的耐药性。
Hepatol Int. 2023 Dec;17(6):1500-1518. doi: 10.1007/s12072-023-10565-2. Epub 2023 Jul 17.
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Breast Cancer Res Treat. 2023 Oct;201(3):353-366. doi: 10.1007/s10549-023-07028-5. Epub 2023 Jul 11.
J Biomol Struct Dyn. 2022 Oct;40(17):7915-7925. doi: 10.1080/07391102.2021.1904005. Epub 2021 Mar 29.
4
Pan cancer patterns of allelic imbalance from chromosomal alterations in 33 tumor types.33 种肿瘤类型染色体改变导致的泛癌症等位基因失衡模式。
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Bioinformatics Analysis Identifies IL6ST as a Potential Tumor Suppressor Gene for Triple-Negative Breast Cancer.生物信息学分析鉴定 IL6ST 为三阴性乳腺癌的潜在肿瘤抑制基因。
Reprod Sci. 2021 Aug;28(8):2331-2341. doi: 10.1007/s43032-021-00509-2. Epub 2021 Mar 1.
6
Mex3a promotes oncogenesis through the RAP1/MAPK signaling pathway in colorectal cancer and is inhibited by hsa-miR-6887-3p.Mex3a 通过 RAP1/MAPK 信号通路促进结直肠癌的发生,并且受到 hsa-miR-6887-3p 的抑制。
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UniProt: the universal protein knowledgebase in 2021.UniProt:2021 年的通用蛋白质知识库。
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J Hepatocell Carcinoma. 2020 Nov 11;7:315-330. doi: 10.2147/JHC.S272109. eCollection 2020.
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MEX3A is upregulated in esophageal squamous cell carcinoma (ESCC) and promotes development and progression of ESCC through targeting CDK6.MEX3A 在食管鳞状细胞癌(ESCC)中上调,并通过靶向 CDK6 促进 ESCC 的发展和进展。
Aging (Albany NY). 2020 Nov 14;12(21):21091-21113. doi: 10.18632/aging.103196.