Deciphering FOXM1 regulation: implications for stemness and metabolic adaptations in glioblastoma.

IF 3.5 4区 医学 Q2 ONCOLOGY Medical Oncology Pub Date : 2025-03-03 DOI:10.1007/s12032-025-02639-y
Kumari Swati, Saniya Arfin, Kirti Agrawal, Saurabh Kumar Jha, Ramya Lakshmi Rajendran, Anand Prakash, Dhruv Kumar, Prakash Gangadaran, Byeong-Cheol Ahn
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Abstract

The Forkhead box M1 (FOXM1) gene-mediated Wnt signaling pathway plays a significant role in the development and growth of glioblastoma multiforme (GBM), an exceptionally aggressive form of brain cancer. Our research explores the crucial involvement of the FOXM1 gene, a key transcription factor within the Wnt signaling pathway using bioinformatics techniques in both GBM and glioma stem cells (GSCs). Elevated FOXM1 gene expression is strongly associated with poor patient survival in GBM. Furthermore, FOXM1 gene expression is correlated with stemness-related factors, such as SOX2 and SOX9, which act as key drivers in the progression of cancer stem cells. Moreover, we specifically look into the direct associations of the FOXM1 gene with angiogenetic-related factors, metabolic genes, metastatic genes, pluripotency-related factors, immune cell infiltration, transcriptional networks, and functional category enrichment analysis, shedding light on the intricate molecular mechanisms involved in GBM initiation and progression. Additionally, our research identifies FOXM1-targeting miRNAs, revealing their potential as therapeutic candidates with implications for patient survival rates and DNA methylation patterns of the FOXM1 gene, uncovering insights into its epigenetic regulation. This knowledge contributes to a comprehensive understanding of the molecular landscape and potential avenues for developing more effective therapeutic approaches against GBM and GSCs.

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解读FOXM1调控:对胶质母细胞瘤的干性和代谢适应的影响。
叉头盒M1 (FOXM1)基因介导的Wnt信号通路在多形性胶质母细胞瘤(GBM)的发展和生长中起着重要作用,GBM是一种异常侵袭性的脑癌。我们的研究利用生物信息学技术探讨了FOXM1基因(Wnt信号通路中的关键转录因子)在GBM和胶质瘤干细胞(GSCs)中的关键作用。FOXM1基因表达升高与GBM患者生存不良密切相关。此外,FOXM1基因表达与干细胞相关因子相关,如SOX2和SOX9,它们在癌症干细胞的进展中起关键驱动作用。此外,我们专门研究了FOXM1基因与血管生成相关因子、代谢基因、转移基因、多能性相关因子、免疫细胞浸润、转录网络和功能类别富集分析的直接关联,揭示了GBM发生和发展的复杂分子机制。此外,我们的研究确定了FOXM1靶向mirna,揭示了它们作为治疗候选物的潜力,对患者生存率和FOXM1基因的DNA甲基化模式有影响,揭示了其表观遗传调控的见解。这些知识有助于全面了解分子景观和开发针对GBM和GSCs的更有效治疗方法的潜在途径。
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来源期刊
Medical Oncology
Medical Oncology 医学-肿瘤学
CiteScore
4.20
自引率
2.90%
发文量
259
审稿时长
1.4 months
期刊介绍: Medical Oncology (MO) communicates the results of clinical and experimental research in oncology and hematology, particularly experimental therapeutics within the fields of immunotherapy and chemotherapy. It also provides state-of-the-art reviews on clinical and experimental therapies. Topics covered include immunobiology, pathogenesis, and treatment of malignant tumors.
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