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全癌分析结合实验预测NNMT作为人类癌症的治疗靶点。

Pan-cancer analysis combined with experiments predicts NNMT as a therapeutic target for human cancers.

作者信息

Huang Hua, Su Lianchun, Zhang Ruihao, Wu Di, Ding Chen, Chen Chen, Zhu Guangsheng, Cao Peijun, Li Xuanguang, Li Yongwen, Liu Hongyu, Chen Jun

机构信息

Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, China.

Department of Thoracic Surgery, First Affiliated Hospital of Shihezi University School of Medicine, Shihezi, China.

出版信息

Discov Oncol. 2024 May 29;15(1):196. doi: 10.1007/s12672-024-01052-7.

DOI:10.1007/s12672-024-01052-7
PMID:38809277
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11136932/
Abstract

The identification of effective therapeutic targets plays a pivotal role in advancing cancer treatment outcomes. We employed a comprehensive pan-cancer analysis, complemented by experimental validation, to explore the potential of Nicotinamide N-methyltransferase (NNMT) as a promising therapeutic strategy for human cancers. By analyzing large-scale transcriptomic datasets across various cancer types, we consistently observed upregulated expression of NNMT. Furthermore, elevated NNMT expression correlated with inferior overall survival in multiple cancer cohorts, underscoring its significance as a prognostic biomarker. Additionally, we investigated the relationship between NNMT expression and the tumor immune microenvironment, which plays a crucial role in regulating anti-tumor immune responses. To confirm the malignant functions of NNMT in tumor cells, we conducted a series of cell-based experiments, revealing that NNMT promotes cancer cell proliferation and invasion, indicative of its oncogenic properties. The integration of computational analysis and experimental validation in our study firmly establishes NNMT as a potential therapeutic target for human cancers. Specifically, targeting NNMT holds promise for the development of innovative and effective cancer treatments. Further investigations into NNMT's role in cancer pathogenesis could potentially pave the way for groundbreaking advancements in cancer treatment.

摘要

确定有效的治疗靶点在提高癌症治疗效果方面起着关键作用。我们采用了全面的泛癌分析,并辅以实验验证,以探索烟酰胺N-甲基转移酶(NNMT)作为一种有前景的人类癌症治疗策略的潜力。通过分析多种癌症类型的大规模转录组数据集,我们一致观察到NNMT表达上调。此外,在多个癌症队列中,NNMT表达升高与较差的总生存期相关,这突出了其作为预后生物标志物的重要性。此外,我们研究了NNMT表达与肿瘤免疫微环境之间的关系,肿瘤免疫微环境在调节抗肿瘤免疫反应中起着关键作用。为了证实NNMT在肿瘤细胞中的恶性功能,我们进行了一系列基于细胞的实验,结果表明NNMT促进癌细胞增殖和侵袭,表明其具有致癌特性。我们研究中计算分析与实验验证的结合,坚定地确立了NNMT作为人类癌症潜在治疗靶点的地位。具体而言,靶向NNMT有望开发出创新有效的癌症治疗方法。对NNMT在癌症发病机制中的作用进行进一步研究,可能为癌症治疗带来突破性进展铺平道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b031/11136932/862a4b6cdc06/12672_2024_1052_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b031/11136932/ddefe7facbef/12672_2024_1052_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b031/11136932/5b9e84f51643/12672_2024_1052_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b031/11136932/7bab6af40eb4/12672_2024_1052_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b031/11136932/dffb0baf572c/12672_2024_1052_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b031/11136932/d4be39d30b10/12672_2024_1052_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b031/11136932/eabcb0326e43/12672_2024_1052_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b031/11136932/a4b558475215/12672_2024_1052_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b031/11136932/862a4b6cdc06/12672_2024_1052_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b031/11136932/ddefe7facbef/12672_2024_1052_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b031/11136932/5b9e84f51643/12672_2024_1052_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b031/11136932/7bab6af40eb4/12672_2024_1052_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b031/11136932/dffb0baf572c/12672_2024_1052_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b031/11136932/d4be39d30b10/12672_2024_1052_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b031/11136932/eabcb0326e43/12672_2024_1052_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b031/11136932/a4b558475215/12672_2024_1052_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b031/11136932/862a4b6cdc06/12672_2024_1052_Fig8_HTML.jpg

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本文引用的文献

1
Nicotinamide N-methyl transferase and cancer-associated thrombosis: insights to prevention and management.烟酰胺 N-甲基转移酶与癌症相关性血栓形成:预防和管理的新视角。
Epigenomics. 2023 Mar;15(6):385-395. doi: 10.2217/epi-2023-0078. Epub 2023 May 22.
2
NNMT Is an Immune-Related Prognostic Biomarker That Modulates the Tumor Microenvironment in Pan-Cancer.神经正五聚体蛋白 1 是一种与免疫相关的预后生物标志物,可调节泛癌中的肿瘤微环境。
Dis Markers. 2023 Feb 9;2023:9226712. doi: 10.1155/2023/9226712. eCollection 2023.
3
Systematic pan-cancer analysis of the nicotinamide n-methyltransferase in human cancer.
人类癌症中烟酰胺N-甲基转移酶的系统性泛癌分析。
Front Genet. 2022 Oct 26;13:1000515. doi: 10.3389/fgene.2022.1000515. eCollection 2022.
4
NNMT-DNMT1 Axis is Essential for Maintaining Cancer Cell Sensitivity to Oxidative Phosphorylation Inhibition.NNMT-DNMT1轴对于维持癌细胞对氧化磷酸化抑制的敏感性至关重要。
Adv Sci (Weinh). 2022 Nov 16;10(1):e2202642. doi: 10.1002/advs.202202642.
5
NNMT contributes to high metastasis of triple negative breast cancer by enhancing PP2A/MEK/ERK/c-Jun/ABCA1 pathway mediated membrane fluidity.神经正五聚体蛋白 N 端甲基转移酶通过增强 PP2A/MEK/ERK/c-Jun/ABCA1 通路介导的膜流动性促进三阴性乳腺癌的高转移。
Cancer Lett. 2022 Oct 28;547:215884. doi: 10.1016/j.canlet.2022.215884. Epub 2022 Aug 19.
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Overexpression of NNMT in Glioma Aggravates Tumor Cell Progression: An Emerging Therapeutic Target.NNMT在胶质瘤中的过表达加剧肿瘤细胞进展:一个新兴的治疗靶点。
Cancers (Basel). 2022 Jul 21;14(14):3538. doi: 10.3390/cancers14143538.
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Nicotinamide N-Methyltransferase: A Promising Biomarker and Target for Human Cancer Therapy.烟酰胺N-甲基转移酶:一种有前景的人类癌症治疗生物标志物和靶点。
Front Oncol. 2022 Jun 9;12:894744. doi: 10.3389/fonc.2022.894744. eCollection 2022.
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Curcumin Reverses NNMT-Induced 5-Fluorouracil Resistance via Increasing ROS and Cell Cycle Arrest in Colorectal Cancer Cells.姜黄素通过增加 ROS 和细胞周期停滞逆转 NNMT 诱导的结直肠癌细胞对 5-氟尿嘧啶的耐药性。
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