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Published on: September 27, 2024
MCM5 is a Novel Therapeutic Target for Glioblastoma
Jian Zhou1,2, Housheng Zheng1, Huiru Zhang1
1Hyperbaric Oxygen Department, International Cancer Center, Shenzhen University General Hospital, Shenzhen University Medical School, Shenzhen, 518055, People's Republic of China.
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.
Insights
Minichromosome maintenance complex component 5 (MCM5) promotes glioblastoma (GBM) cell proliferation and chemotherapy resistance. Understanding MCM5's role offers new therapeutic strategies and improves prognosis prediction for GBM patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Minichromosome maintenance complex component 5 (MCM5) is a DNA licensing factor and a known biomarker in various cancers.
- Its specific role in glioblastoma (GBM) and its therapeutic implications remain incompletely understood.
Purpose of the Study:
- To investigate the role of MCM5 in glioblastoma (GBM) treatment.
- To elucidate the underlying mechanisms of MCM5 in GBM.
- To identify MCM5 as a potential therapeutic target and prognostic biomarker.
Main Methods:
- Analysis of transcriptomic and proteomic data from TCGA and CPTAC databases for GBM patients.
- Identification of differentially expressed genes in chemotherapy-treated GBM tissues using DeSeq2.
- Development of a prognostic risk score model via Cox regression analyses.
- In vitro knockdown and overexpression studies of MCM5 in GBM cells.
- Investigation of MCM5's upstream regulatory factors and analysis of immune cell infiltration and drug sensitivity.
Main Results:
- Consistent alterations in gene expression (46 upregulated, 94 downregulated) were observed in chemotherapy-treated GBM samples at mRNA and protein levels.
- MCM5 was identified as a prognostic and potentially therapeutic gene in GBM.
- Increased MCM5 expression promoted GBM cell proliferation and resistance to temozolomide (TMZ) in vitro.
- Associations between MCM5 and transcription factors (CREB1, CTCF, NFYB, NRF1, PBX1, TEAD1, USF1) were identified.
- Differences in immune cell infiltration and drug sensitivity were observed across risk groups.
Conclusions:
- MCM5 plays a significant role in glioblastoma (GBM) pathogenesis.
- MCM5 is a prognostic biomarker and a potential therapeutic target in GBM.
- Elucidating MCM5's function provides insights for developing novel GBM treatment strategies and predicting patient outcomes.
