Abstract
Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with limited treatment options and a poor prognosis. Its defining features include rapid proliferation, invasive capacity, and resistance to therapy. Bioinformatics analyses using TCGA and UALCAN datasets were conducted to assess MXRA8 and ELF3 expression and their association with patient survival. The expression levels were validated through qPCR and western blotting. Functional assays, including proliferation, migration, and invasion tests, were performed after silencing or overexpressing MXRA8 and ELF3. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays determined ELF3’s role in regulating MXRA8 transcription. An in vivo xenograft model was used to evaluate the effects of ELF3 and MXRA8 on tumor growth. MXRA8 expression was significantly elevated in GBM tissues and associated with reduced overall survival. Functional analyses revealed that MXRA8 knockdown inhibited oncogenic traits. Moreover, ELF3 was overexpressed in GBM tissues and positively correlated with MXRA8 expression. ChIP and dual-luciferase assays confirmed that ELF3 binds to the MXRA8 promoter and activates its transcription. Rescue experiments showed that MXRA8 overexpression could reverse the tumor-suppressive effects of ELF3 knockdown. In vivo, silencing ELF3 or MXRA8 inhibited tumor growth and proliferation. This study suggests that the ELF3-MXRA8 axis may be a critical driver of GBM progression, with ELF3 promoting tumor growth and invasion through transcriptional activation of MXRA8.
Data availability
The datasets generated and analysed during the current study are available in [https://doi.org/10.7910/DVN/UFHS7Z](https:/doi.org/10.7910/DVN/UFHS7Z) . Additional information and resources can be obtained by contacting the corresponding authors upon request.
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Funding
This study was funded by the National Natural Science Foundation of China (Grant No. 82303915).
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Maomao Wang, Haiji Bo, Dapeng Chen contributed to data curation, wrote the original draft, prepared the visualization, conducted the investigation, and validated the findings. Jiangxin Mao contributed to formal analysis, visualization, and investigation. Zong Miao and Laixing Wang oversaw project administration and reviewed and edited the manuscript. Zong Miao conceptualized the study, developed the methodology, created visualizations, and reviewed and edited the manuscript. Laixing Wang provided supervision, secured funding, and reviewed and edited the manuscript. All authors gave final approval for the manuscript.
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The study involving human participants adhered to ethical standards set by the institutional and/or research committee in accordance with the 1975 Declaration of Helsinki (revised in 2013). The animal experimental protocol followed the Guide for the Care and Use of Laboratory Animals, 8th Edition, and the study was reported in compliance with ARRIVE guidelines.
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Wang, M., Bo, H., Chen, D. et al. ELF3 drives glioblastoma multiforme progression through the regulation of MXRA8 expression. Sci Rep (2026). https://doi.org/10.1038/s41598-026-46657-w
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DOI: https://doi.org/10.1038/s41598-026-46657-w
