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泛癌分析揭示了NEDDylation修饰在肿瘤发生中的作用和机制。

Pan-cancer analysis unveils the role and mechanisms of neddylation modifications in tumorigenesis.

作者信息

Hu Qianhua, Li Xiang, Wang Ping, Xie Ying

机构信息

Key Laboratory of Molecular Epidemiology of Hunan Province, School of Public Health, Health Science Center, Hunan Normal University, Changsha, China.

出版信息

Med Oncol. 2025 Mar 19;42(4):119. doi: 10.1007/s12032-025-02658-9.

DOI:10.1007/s12032-025-02658-9
PMID:40106140
Abstract

This study explores the roles of ubiquitin-like modification genes in pan-cancer, focusing on their regulatory mechanisms, prognostic implications, and drug sensitivity. Data on five key neddylation pathway genes (RBX1, NEDD8, NAE1, UBA3, UBE2M) were collected from TCGA and GTEx databases, covering mRNA expression, DNA methylation, SNVs, and CNVs. Gene expression differences between normal and cancer tissues, along with associations with genetic alterations, methylation, and cancer-related pathways, were analyzed. Drug sensitivity correlations were assessed using GDSC and CTRP databases. Neddylation pathway genes exhibit hypomethylation and overexpression across various cancers, correlating with poor prognosis. SNVs are predominantly missense mutations, while CNVs are mostly heterozygous deletions and amplifications. These genes regulate several key cancer-related pathways, such as DNA damage repair, cell cycle modulation, and inhibition of RTK/RAS/MAPK pathways. Ubiquitin-like modification genes are associated with poor prognosis due to their low methylation and high expression in cancers. Their genetic alterations impact cancer pathways, underscoring their potential as therapeutic targets and prognostic biomarkers.

摘要

本研究探讨类泛素修饰基因在泛癌中的作用,重点关注其调控机制、预后意义和药物敏感性。从TCGA和GTEx数据库收集了五个关键的NEDD化途径基因(RBX1、NEDD8、NAE1、UBA3、UBE2M)的数据,涵盖mRNA表达、DNA甲基化、单核苷酸变异(SNV)和拷贝数变异(CNV)。分析了正常组织和癌组织之间的基因表达差异,以及与基因改变、甲基化和癌症相关途径的关联。使用GDSC和CTRP数据库评估药物敏感性相关性。NEDD化途径基因在各种癌症中表现出低甲基化和过表达,与不良预后相关。SNV主要为错义突变,而CNV大多为杂合缺失和扩增。这些基因调控多个关键的癌症相关途径,如DNA损伤修复、细胞周期调节以及RTK/RAS/MAPK途径的抑制。类泛素修饰基因因其在癌症中的低甲基化和高表达而与不良预后相关。它们的基因改变影响癌症途径,凸显了它们作为治疗靶点和预后生物标志物的潜力。

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本文引用的文献

1
Evaluating the Role of Neddylation Modifications in Kidney Renal Clear Cell Carcinoma: An Integrated Approach Using Bioinformatics, MLN4924 Dosing Experiments, and RNA Sequencing.评估Neddylation修饰在肾透明细胞癌中的作用:一种结合生物信息学、MLN4924给药实验和RNA测序的综合方法。
Pharmaceuticals (Basel). 2024 May 15;17(5):635. doi: 10.3390/ph17050635.
2
Protein neddylation and its role in health and diseases.蛋白质的类泛素化及其在健康和疾病中的作用。
Signal Transduct Target Ther. 2024 Apr 5;9(1):85. doi: 10.1038/s41392-024-01800-9.
3
Bioinformatics analysis of a disease-specific lncRNA-miRNA-mRNA regulatory network in recurrent spontaneous abortion (RSA).
疾病特异性 lncRNA-miRNA-mRNA 调控网络在复发性自然流产(RSA)中的生物信息学分析。
Arch Gynecol Obstet. 2024 Apr;309(4):1609-1620. doi: 10.1007/s00404-023-07356-3. Epub 2024 Feb 4.
4
Deciphering the role of neddylation in tumor microenvironment modulation: common outcome of multiple signaling pathways.解析NEDDylation在肿瘤微环境调节中的作用:多种信号通路的共同结果
Biomark Res. 2024 Jan 8;12(1):5. doi: 10.1186/s40364-023-00545-x.
5
Targeting cullin neddylation for cancer and fibrotic diseases.靶向泛素化用于癌症和纤维化疾病。
Theranostics. 2023 Sep 4;13(14):5017-5056. doi: 10.7150/thno.78876. eCollection 2023.
6
FOXO1-regulated lncRNA CYP1B1-AS1 suppresses breast cancer cell proliferation by inhibiting neddylation.FOXO1 调控的长链非编码 RNA CYP1B1-AS1 通过抑制泛素化来抑制乳腺癌细胞增殖。
Breast Cancer Res Treat. 2023 Nov;202(2):397-408. doi: 10.1007/s10549-023-07090-z. Epub 2023 Aug 28.
7
NEDD8-conjugating enzyme E2s: critical targets for cancer therapy.NEDD8缀合酶E2s:癌症治疗的关键靶点。
Cell Death Discov. 2023 Jan 23;9(1):23. doi: 10.1038/s41420-023-01337-w.
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Neddylation of HER2 Inhibits its Protein Degradation and promotes Breast Cancer Progression.HER2 的泛素化抑制其蛋白降解并促进乳腺癌进展。
Int J Biol Sci. 2023 Jan 1;19(2):377-392. doi: 10.7150/ijbs.75852. eCollection 2023.
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