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

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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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Authors and Affiliations

  1. Department of Biotechnology, School of Life Science, Mahatma Gandhi Central University. Motihari, Bihar, 845401, India

    Kumari Swati & Anand Prakash

  2. School of Health Sciences and Technology, UPES, Dehradun, Uttrakhand, 248007, India

    Saniya Arfin, Kirti Agrawal & Dhruv Kumar

  3. Department of Zoology, Kalindi College, University of Delhi, New Delhi, 110008, India

    Saurabh Kumar Jha

  4. Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea

    Ramya Lakshmi Rajendran, Prakash Gangadaran & Byeong-Cheol Ahn

  5. Cardiovascular Research Institute, Kyungpook National University, Daegu, 41944, Republic of Korea

    Ramya Lakshmi Rajendran, Prakash Gangadaran & Byeong-Cheol Ahn

  6. BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea

    Ramya Lakshmi Rajendran, Prakash Gangadaran & Byeong-Cheol Ahn

  7. Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, 41944, Republic of Korea

    Byeong-Cheol Ahn

  8. Centre For Himalayan Studies, University Enclave, Delhi, 110007, India

    Saurabh Kumar Jha

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Contributions

Kumari Swati, Saniya Arfin, Kirti Agrawal, Saurabh Kumar Jha and Ramya Lakshmi Rajendran drafted, wrote, and edited this manuscript. Anand Prakash, Dhruv Kumar, Prakash Gangadaran and Byeong-Cheol Ahn edited and supervised this manuscript.

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Swati, K., Arfin, S., Agrawal, K. et al. Deciphering FOXM1 regulation: implications for stemness and metabolic adaptations in glioblastoma. Med Oncol 42, 88 (2025). https://doi.org/10.1007/s12032-025-02639-y

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