{"title":"High MCM10 expression mediates TMZ resistance and promotes the progression of glioma.","authors":"Qiusi Tian, Zhijun Bao, Yifei Zhao, Qun Zhang","doi":"10.1007/s00280-025-04807-3","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>In glioblastoma, the heterogeneity of tumors often complicates treatment outcomes, particularly resistance to temozolomide (TMZ). This study aimed to investigate the expression characteristics of MCM10 in gliomas and its potential role in TMZ resistance.</p><p><strong>Methods: </strong>Analyze the expression of MCM10 in glioma cells within the datasets Glioma_GSE102130, Glioma_GSE130224, Glioma_GSE131928_10X, and Glioma_GSE131928_Smartseq2 using the TISCH2 single-cell database.Subsequently, the expression level of MCM10 was evaluated using the TMZ-resistant cell lines U251-TR and LN229-TR. Glioma cells with reduced MCM10 expression were constructed through lentiviral interference.Construct glioma cells with MCM10 knockdown through lentiviral interference. Additionally, this study conducts an association analysis between MCM10 expression and patterns of DNA methylation and RNA methylation.Finally, the function of MCM10 was validated in a heterotopic mouse model.</p><p><strong>Results: </strong>MCM10 mRNA is highly expressed in osteoclast-like malignant cells (OC-likemalignant cells) and oligodendrocyte progenitor-like malignant cells (OPC-like malignant cells). After treatment with TMZ, the levels of MCM10 protein and mRNA significantly increased. Knocking down MCM10 significantly reduced the migration and invasion of U251 and LN229 cells, while altering the expression of molecular markers associated with epithelial-mesenchymal transition (EMT). Weighted gene co-expression network analysis (WGCNA) revealed signaling pathways associated with drug resistance and identified overlapping differentially expressed mRNAs between resistant cells and MCM10 knockdown cells. High expression of MCM10 is associated with low DNA methylation, and MCM10 methylation is positively correlated with patient survival rates. Furthermore, inhibition of MCM10 significantly slowed tumor growth, indicating its potential as a therapeutic target for gliomas.</p><p><strong>Conclusion: </strong>MCM 10 is a key mediator of TMZ resistance in glioblastoma.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"93"},"PeriodicalIF":2.3000,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Chemotherapy and Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00280-025-04807-3","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: In glioblastoma, the heterogeneity of tumors often complicates treatment outcomes, particularly resistance to temozolomide (TMZ). This study aimed to investigate the expression characteristics of MCM10 in gliomas and its potential role in TMZ resistance.
Methods: Analyze the expression of MCM10 in glioma cells within the datasets Glioma_GSE102130, Glioma_GSE130224, Glioma_GSE131928_10X, and Glioma_GSE131928_Smartseq2 using the TISCH2 single-cell database.Subsequently, the expression level of MCM10 was evaluated using the TMZ-resistant cell lines U251-TR and LN229-TR. Glioma cells with reduced MCM10 expression were constructed through lentiviral interference.Construct glioma cells with MCM10 knockdown through lentiviral interference. Additionally, this study conducts an association analysis between MCM10 expression and patterns of DNA methylation and RNA methylation.Finally, the function of MCM10 was validated in a heterotopic mouse model.
Results: MCM10 mRNA is highly expressed in osteoclast-like malignant cells (OC-likemalignant cells) and oligodendrocyte progenitor-like malignant cells (OPC-like malignant cells). After treatment with TMZ, the levels of MCM10 protein and mRNA significantly increased. Knocking down MCM10 significantly reduced the migration and invasion of U251 and LN229 cells, while altering the expression of molecular markers associated with epithelial-mesenchymal transition (EMT). Weighted gene co-expression network analysis (WGCNA) revealed signaling pathways associated with drug resistance and identified overlapping differentially expressed mRNAs between resistant cells and MCM10 knockdown cells. High expression of MCM10 is associated with low DNA methylation, and MCM10 methylation is positively correlated with patient survival rates. Furthermore, inhibition of MCM10 significantly slowed tumor growth, indicating its potential as a therapeutic target for gliomas.
Conclusion: MCM 10 is a key mediator of TMZ resistance in glioblastoma.
期刊介绍：
Addressing a wide range of pharmacologic and oncologic concerns on both experimental and clinical levels, Cancer Chemotherapy and Pharmacology is an eminent journal in the field. The primary focus in this rapid publication medium is on new anticancer agents, their experimental screening, preclinical toxicology and pharmacology, single and combined drug administration modalities, and clinical phase I, II and III trials. It is essential reading for pharmacologists and oncologists giving results recorded in the following areas: clinical toxicology, pharmacokinetics, pharmacodynamics, drug interactions, and indications for chemotherapy in cancer treatment strategy.
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