Unlocking the secret of glioblastoma multiforme: the role of lactylation in tumor progression, drug resistance and immune microenvironment.

IF 6 2区 医学 Q1 ONCOLOGY
Yifei Xiao, Ruipeng Zheng, Fengjun Lv, Guang Yang, Haitao Ge, Mingchun Yang, Kan Wang, Yu Cheng
{"title":"Unlocking the secret of glioblastoma multiforme: the role of lactylation in tumor progression, drug resistance and immune microenvironment.","authors":"Yifei Xiao, Ruipeng Zheng, Fengjun Lv, Guang Yang, Haitao Ge, Mingchun Yang, Kan Wang, Yu Cheng","doi":"10.1186/s12935-025-03933-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma multiforme (GBM), the most prevalent and lethal type of brain cancer, is characterized by a poor prognosis despite advancements in comprehensive treatments, including surgery, chemotherapy, and radiotherapy. Lactylation, an emerging epigenetic modification, has been shown to influence the biological behavior of tumor cells; however, its role in GBM remains to be further elucidated.</p><p><strong>Methods: </strong>In this study, we analyzed the relationship between lactylation-related genes (LRGs) and malignant biological behavior, temozolomide resistance, and the immune microenvironment of GBM using scRNA-seq data from public databases. Subsequently, we identified temozolomide-resistant lactylation-related genes (TMZR-LRGs) through differential gene expression analysis. Based on these genes, we proceeded to classify GBM subtypes and establish a risk prediction model to assess patient prognosis and treatment response. Finally, we validated the impact of lactylation on TMZ resistance and malignant biological behavior of GBM both in vivo and in vitro by knocking out UBE2E1 to increase cellular lactylation levels.</p><p><strong>Result: </strong>ScRNA-seq analysis and in vivo and in vitro experiments both demonstrated that lactylation was significantly up-regulated in GBM cells. In the GBM subtype, MES-like cells have the highest lactylation level. Furthermore, an increase in lactylation levels enhanced the malignant proliferation and temozolomide resistance of GBM cells. The risk model based on TMZR-LRGs effectively predicted the prognosis and immune characteristics of GBM patients and had the potential to accurately identify targeted therapeutic drugs for GBM.</p><p><strong>Conclusion: </strong>Lactylation is critical for malignant progression, temozolomide resistance and the establishment of an immunosuppressive microenvironment of GBM. The risk model based on lactylation-related genes is an effective tool for assessing the prognosis and treatment response of GBM patients. LRGs have potential as therapeutic targets for GBM, providing a new direction for improving patient outcomes.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"299"},"PeriodicalIF":6.0000,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12330052/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Cell International","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12935-025-03933-5","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Background: Glioblastoma multiforme (GBM), the most prevalent and lethal type of brain cancer, is characterized by a poor prognosis despite advancements in comprehensive treatments, including surgery, chemotherapy, and radiotherapy. Lactylation, an emerging epigenetic modification, has been shown to influence the biological behavior of tumor cells; however, its role in GBM remains to be further elucidated.

Methods: In this study, we analyzed the relationship between lactylation-related genes (LRGs) and malignant biological behavior, temozolomide resistance, and the immune microenvironment of GBM using scRNA-seq data from public databases. Subsequently, we identified temozolomide-resistant lactylation-related genes (TMZR-LRGs) through differential gene expression analysis. Based on these genes, we proceeded to classify GBM subtypes and establish a risk prediction model to assess patient prognosis and treatment response. Finally, we validated the impact of lactylation on TMZ resistance and malignant biological behavior of GBM both in vivo and in vitro by knocking out UBE2E1 to increase cellular lactylation levels.

Result: ScRNA-seq analysis and in vivo and in vitro experiments both demonstrated that lactylation was significantly up-regulated in GBM cells. In the GBM subtype, MES-like cells have the highest lactylation level. Furthermore, an increase in lactylation levels enhanced the malignant proliferation and temozolomide resistance of GBM cells. The risk model based on TMZR-LRGs effectively predicted the prognosis and immune characteristics of GBM patients and had the potential to accurately identify targeted therapeutic drugs for GBM.

Conclusion: Lactylation is critical for malignant progression, temozolomide resistance and the establishment of an immunosuppressive microenvironment of GBM. The risk model based on lactylation-related genes is an effective tool for assessing the prognosis and treatment response of GBM patients. LRGs have potential as therapeutic targets for GBM, providing a new direction for improving patient outcomes.

揭开多形性胶质母细胞瘤的秘密:乳酸化在肿瘤进展、耐药和免疫微环境中的作用。
背景:多形性胶质母细胞瘤(GBM)是最常见和最致命的脑癌类型,尽管在手术、化疗和放疗等综合治疗方面取得了进展,但其预后较差。乳酸酰化是一种新兴的表观遗传修饰,已被证明可以影响肿瘤细胞的生物学行为;然而,其在GBM中的作用仍有待进一步阐明。方法:本研究利用公共数据库的scRNA-seq数据,分析乳酸化相关基因(LRGs)与GBM恶性生物学行为、替莫唑胺耐药性和免疫微环境的关系。随后,我们通过差异基因表达分析鉴定了替莫唑胺耐药乳酸化相关基因(TMZR-LRGs)。基于这些基因,我们继续对GBM亚型进行分类,并建立风险预测模型来评估患者预后和治疗反应。最后,我们通过敲除UBE2E1以增加细胞乳酸化水平,验证了乳酸化对体内和体外GBM TMZ耐药和恶性生物学行为的影响。结果:ScRNA-seq分析和体内、体外实验均表明,GBM细胞的乳酸化水平明显上调。在GBM亚型中,mes样细胞的乳酸化水平最高。此外,乳酸化水平的增加增强了GBM细胞的恶性增殖和替莫唑胺耐药性。基于TMZR-LRGs的风险模型能够有效预测GBM患者的预后和免疫特性,具有准确识别GBM靶向治疗药物的潜力。结论:乳酸化是恶性进展、替莫唑胺耐药和GBM免疫抑制微环境建立的关键。基于乳酸酰化相关基因的风险模型是评估GBM患者预后和治疗反应的有效工具。LRGs有潜力成为GBM的治疗靶点,为改善患者预后提供了新的方向。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
10.90
自引率
1.70%
发文量
360
审稿时长
1 months
期刊介绍: Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信