MCM5 是胶质母细胞瘤的新型治疗靶点
IF 2.7
4区 医学
Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
引用次数: 0
摘要
目的：MCM5 是一种参与细胞增殖的 DNA 许可因子：MCM5 是一种参与细胞增殖的 DNA 许可因子，以前曾被确定为多种恶性肿瘤的优良生物标志物。然而，MCM5 在 GBM 中的作用尚未完全明确。本研究旨在探究 MCM5 在 GBM 治疗中的潜在作用，并阐明其潜在机制，这有利于开发新的治疗策略和预测预后：首先，我们从 TCGA 和 CPTAC 数据库中获得了胶质瘤患者的转录组和蛋白质组数据。方法：首先，我们从 TCGA 和 CPTAC 数据库中获取了胶质瘤患者的转录组和蛋白质组数据，然后利用 DeSeq2 R 软件包确定了化疗后 GBM 组织中具有联合差异表达的基因。为了建立预后风险评分模型，我们进行了单变量和多变量 Cox 回归分析。我们利用体外敲除和过表达 MCM5 来进一步研究 GBM 细胞的生物学功能。此外，我们还深入研究了 MCM5 的上游调控，发现其与多个转录因子存在关联。最后，我们还研究了预后风险模型中确定的不同风险群体在免疫细胞浸润和药物敏感性方面的差异：在这项研究中，化疗后的 GBM 样本在 mRNA 和蛋白质水平上表现出 46 个上调基因和 94 个下调基因的一致改变。值得注意的是，MCM5 是一个具有预后意义和潜在治疗相关性的基因。体外实验随后验证了 MCM5 表达的增加在促进 GBM 细胞增殖和对 TMZ 产生抗药性方面的作用。在上游调控分析中发现了与 CREB1、CTCF、NFYB、NRF1、PBX1、TEAD1 和 USF1 等转录因子的相关性，丰富了我们对 MCM5 调控机制的理解。该研究还深入研究了免疫细胞浸润和药物敏感性，为个性化治疗方法提供了有价值的见解：本研究确定了 MCM5 在 GBM 中的关键作用，通过阐明其在促进细胞增殖和化疗耐药性方面的作用，证明了其预后意义和潜在的治疗相关性。 关键词：胶质母细胞瘤；迷你染色体维护蛋白 5；化疗耐药性本文章由计算机程序翻译，如有差异，请以英文原文为准。
MCM5 is a Novel Therapeutic Target for Glioblastoma
Objective: MCM5 is a DNA licensing factor involved in cell proliferation and has been previously established as an excellent biomarker in a number of malignancies. Nevertheless, the role of MCM5 in GBM has not been fully clarified. The present study aimed to investigate the potential roles of MCM5 in the treatment of GBM and to elucidate its underlying mechanism, which is beneficial for developing new therapeutic strategies and predicting prognosis.
Methods: Firstly, we obtained transcriptomic and proteomic data from the TCGA and CPTAC databases on glioma patients. Employing the DeSeq2 R package, we then identified genes with joint differential expression in GBM tissues subjected to chemotherapy. To develop a prognostic risk score model, we performed univariate and multivariate Cox regression analyses. In vitro knockdown and overexpression of MCM5 were used to further investigate the biological functions of GBM cells. Additionally, we also delved into the upstream regulation of MCM5, revealing associations with several transcription factors. Finally, we investigated differences in immune cell infiltration and drug sensitivity across diverse risk groups identified in the prognostic risk model.
Results: In this study, the chemotherapy-treated GBM samples exhibited consistent alterations in 46 upregulated and 94 downregulated genes at both the mRNA and protein levels. Notably, MCM5 emerged as a gene with prognostic significance as well as potential therapeutic relevance. In vitro experiments subsequently validated the role of increased MCM5 expression in promoting GBM cell proliferation and resistance to TMZ. Correlations with transcription factors such as CREB1, CTCF, NFYB, NRF1, PBX1, TEAD1, and USF1 were discovered during upstream regulatory analysis, enriching our understanding of MCM5 regulatory mechanisms. The study additionally delves into immune cell infiltration and drug sensitivity, providing valuable insights for personalized treatment approaches.
Conclusion: This study identifies MCM5 as a key player in GBM, demonstrating its prognostic significance and potential therapeutic relevance by elucidating its role in promoting cell proliferation and resistance to chemotherapy.
Keywords: glioblastoma, minichromosome maintenance protein 5, chemotherapeutic drug resistance
Methods: Firstly, we obtained transcriptomic and proteomic data from the TCGA and CPTAC databases on glioma patients. Employing the DeSeq2 R package, we then identified genes with joint differential expression in GBM tissues subjected to chemotherapy. To develop a prognostic risk score model, we performed univariate and multivariate Cox regression analyses. In vitro knockdown and overexpression of MCM5 were used to further investigate the biological functions of GBM cells. Additionally, we also delved into the upstream regulation of MCM5, revealing associations with several transcription factors. Finally, we investigated differences in immune cell infiltration and drug sensitivity across diverse risk groups identified in the prognostic risk model.
Results: In this study, the chemotherapy-treated GBM samples exhibited consistent alterations in 46 upregulated and 94 downregulated genes at both the mRNA and protein levels. Notably, MCM5 emerged as a gene with prognostic significance as well as potential therapeutic relevance. In vitro experiments subsequently validated the role of increased MCM5 expression in promoting GBM cell proliferation and resistance to TMZ. Correlations with transcription factors such as CREB1, CTCF, NFYB, NRF1, PBX1, TEAD1, and USF1 were discovered during upstream regulatory analysis, enriching our understanding of MCM5 regulatory mechanisms. The study additionally delves into immune cell infiltration and drug sensitivity, providing valuable insights for personalized treatment approaches.
Conclusion: This study identifies MCM5 as a key player in GBM, demonstrating its prognostic significance and potential therapeutic relevance by elucidating its role in promoting cell proliferation and resistance to chemotherapy.
Keywords: glioblastoma, minichromosome maintenance protein 5, chemotherapeutic drug resistance
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来源期刊
OncoTargets and therapy
BIOTECHNOLOGY & APPLIED MICROBIOLOGY-ONCOLOGY
CiteScore
9.70
自引率
0.00%
发文量
221
审稿时长
1 months
期刊介绍：
OncoTargets and Therapy is an international, peer-reviewed journal focusing on molecular aspects of cancer research, that is, the molecular diagnosis of and targeted molecular or precision therapy for all types of cancer.
The journal is characterized by the rapid reporting of high-quality original research, basic science, reviews and evaluations, expert opinion and commentary that shed novel insight on a cancer or cancer subtype.
Specific topics covered by the journal include:
-Novel therapeutic targets and innovative agents
-Novel therapeutic regimens for improved benefit and/or decreased side effects
-Early stage clinical trials
Further considerations when submitting to OncoTargets and Therapy:
-Studies containing in vivo animal model data will be considered favorably.
-Tissue microarray analyses will not be considered except in cases where they are supported by comprehensive biological studies involving multiple cell lines.
-Biomarker association studies will be considered only when validated by comprehensive in vitro data and analysis of human tissue samples.
-Studies utilizing publicly available data (e.g. GWAS/TCGA/GEO etc.) should add to the body of knowledge about a specific disease or relevant phenotype and must be validated using the authors’ own data through replication in an independent sample set and functional follow-up.
-Bioinformatics studies must be validated using the authors’ own data through replication in an independent sample set and functional follow-up.
-Single nucleotide polymorphism (SNP) studies will not be considered.
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