NUF2 is associated with cancer stem cell characteristics and a potential drug target for prostate cancer.

IF 3.9 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Frontiers in Molecular Biosciences Pub Date : 2024-12-05 eCollection Date: 2024-01-01 DOI:10.3389/fmolb.2024.1481375

Dongxu Zhang, Pu Liang, Qi Wang, Bowen Xia, Liqian Yu, Xiaopeng Hu

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Abstract

Background: Cancer stem cells are characterized by self-renewal, clonal tumor initiation capacity, and treatment resistance, which play essential roles in the tumor progression of prostate cancer (PCa). In this study, we aim to explore the features of cancer stemness and characterize the expression of stem cell-related genes for PCa.

Methods: We downloaded RNA-seq data and related clinical information from The Cancer Genome Atlas (TCGA) database. The mRNA stemness index (mRNAsi) was analyzed for various clinical features, overall survival (OS), and disease-free survival (DFS), and a weighted gene co-expression network analysis (WGCNA) was performed to identify crucial gene modules and key genes, which may play a role in CSCs. The key gene functions were verified using multiple databases, including the TCGA and Gene Expression Omnibus database (GEO). Next, we explored the potential function of the modules and genes obtained using WGCNA using an enrichment analysis. Finally, we performed in vitro experiments for further verification.

Results: We found that mRNAsi were higher in PCa tissues than in normal tissues, and the mRNAsi were closely related to the clinical characteristics of PCa. A total of 16 key genes associated with the mRNAsi scores were identified by WGCNA analysis, including NCAPG, NEK2, DLGAP5, CENPA, CENPF, TPX2, GTSE1, KIF4A, NEIL3, CDC25C, UBE2C, CDCA5, MELK, SKA3, NUF2, and BIRC5. These genes were explicitly highly expressed in PCa across TCGA cancers and were validated in 3 independent GEO PCa datasets. The functional annotations of the key genes were linked with the cell proliferation processes. NUF2 may be a potential biomarker for PCa. In vitro experiments showed that knockdown NUF2 reduced the proliferation and migration of PCa cells.

Conclusion: The 16 key genes identified in this study significantly correlate with PCa stem cell characteristics and showed prognosis-oriented effects in PCa patients. Further, the NUF2 gene may be used as a drug target for treating PCa.

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NUF2 与癌症干细胞特征有关，是治疗前列腺癌的潜在药物靶点。

背景：肿瘤干细胞具有自我更新、克隆肿瘤启动能力和治疗抵抗能力，在前列腺癌（PCa）的肿瘤进展中发挥重要作用。在本研究中，我们旨在探讨癌的干性特征，并表征癌干细胞相关基因的表达。方法：从美国癌症基因组图谱（TCGA）数据库下载RNA-seq数据及相关临床资料。通过mRNA干性指数（mRNAsi）分析各种临床特征、总生存期（OS）和无病生存期（DFS），并通过加权基因共表达网络分析（WGCNA）确定可能在CSCs中发挥作用的关键基因模块和关键基因。利用TCGA和gene Expression Omnibus数据库（GEO）等多个数据库对关键基因功能进行验证。接下来，我们通过富集分析探讨了利用WGCNA获得的模块和基因的潜在功能。最后，我们进行了体外实验进一步验证。结果：我们发现mRNAsi在PCa组织中高于正常组织，并且mRNAsi与PCa的临床特征密切相关。通过WGCNA分析共鉴定出与mRNAsi评分相关的16个关键基因，包括NCAPG、NEK2、DLGAP5、CENPA、CENPF、TPX2、GTSE1、KIF4A、NEIL3、CDC25C、UBE2C、CDCA5、MELK、SKA3、NUF2和BIRC5。这些基因在TCGA癌的PCa中显式高表达，并在3个独立的GEO PCa数据集中得到验证。关键基因的功能注释与细胞增殖过程有关。NUF2可能是前列腺癌的潜在生物标志物。体外实验表明，敲除NUF2可降低PCa细胞的增殖和迁移。结论：本研究发现的16个关键基因与前列腺癌干细胞特征显著相关，并在前列腺癌患者中显示预后导向作用。此外，NUF2基因可以作为治疗PCa的药物靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Molecular Biosciences Biochemistry, Genetics and Molecular Biology-Biochemistry

CiteScore

7.20

自引率

4.00%

发文量

1361

审稿时长

14 weeks

期刊介绍： Much of contemporary investigation in the life sciences is devoted to the molecular-scale understanding of the relationships between genes and the environment — in particular, dynamic alterations in the levels, modifications, and interactions of cellular effectors, including proteins. Frontiers in Molecular Biosciences offers an international publication platform for basic as well as applied research; we encourage contributions spanning both established and emerging areas of biology. To this end, the journal draws from empirical disciplines such as structural biology, enzymology, biochemistry, and biophysics, capitalizing as well on the technological advancements that have enabled metabolomics and proteomics measurements in massively parallel throughput, and the development of robust and innovative computational biology strategies. We also recognize influences from medicine and technology, welcoming studies in molecular genetics, molecular diagnostics and therapeutics, and nanotechnology. Our ultimate objective is the comprehensive illustration of the molecular mechanisms regulating proteins, nucleic acids, carbohydrates, lipids, and small metabolites in organisms across all branches of life. In addition to interesting new findings, techniques, and applications, Frontiers in Molecular Biosciences will consider new testable hypotheses to inspire different perspectives and stimulate scientific dialogue. The integration of in silico, in vitro, and in vivo approaches will benefit endeavors across all domains of the life sciences.