Abstract
BACKGROUND: TMEM201, a nuclear membrane protein, is thought to play an important role in tumor progression, but its involvement in lower-grade glioma (LGG) remains unclear. This study aims to investigate the impact of TMEM201 expression on the prognosis, clinical characteristics, and biological behaviors of LGG. METHODS: RNA expression data from the TCGA, CGGA, and GEO databases were analyzed to explore the correlation between TMEM201 expression and clinical features of LGG. In vitro and in vivo experiments were conducted to assess the effects of TMEM201 knockdown on cell proliferation, migration, and tumorigenic potential. DNA methylation sites associated with TMEM201 were analyzed, and KEGG pathway enrichment was performed to identify the molecular mechanisms underlying TMEM201’s role in LGG. RESULTS: The analysis showed that high TMEM201 expression was associated with poor prognosis, higher WHO grade, and tumor recurrence in LGG patients. Survival analysis confirmed that elevated TMEM201 levels correlated with shorter survival. Knockdown of TMEM201 in SHG44 cells led to significant inhibition of cell proliferation, migration, and tumor formation in vivo. DNA methylation analysis identified key sites regulating TMEM201 expression, and KEGG analysis revealed pathways such as HIF-1, VEGF, and Notch that contribute to tumor progression. CONCLUSION: TMEM201 acts as a potential oncogene in LGG by influencing key cellular signaling pathways and tumor behaviors. It is an independent risk factor for poor prognosis and may serve as a promising biomarker for diagnosis and personalized treatment. This study provides valuable insights into the molecular mechanisms of LGG progression and highlights TMEM201 as a therapeutic target. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12920-026-02313-w.