Ya-Jui Lin

Supplementary Table 2. Patient demographics of CGGA cohorts.

Supplementary Figure 9. Hypoxia induced SSAT expression in glioma cells and the intracellular GSH levels.

Supplementary Table 3. Cox regression analysis of TCGA cohorts.

Supplementary Table 1. Patient demographics of TCGA cohorts.

Glioblastoma (GBM), a highly aggressive brain tumor, thrives in hypoxic environments. Tumor-derived exosomes are key drivers of glioma progression, facilitating tumor growth, immune evasion, angiogenesis, and therapy resistance. Acrolein, a toxic byproduct produced under hypoxic conditions, causes DNA damage, inflammation, and mitochondrial dysfunction and potentiates oxidative stress. Elevated acrolein levels and associated DNA damage are linked to poor GBM prognosis. This study aims to uncover the role of acrolein in GBM progression through exosome-mediated pathways and the associated molecular mechanisms. We found that acrolein production under hypoxia promotes GBM cell malignant behaviors, such as migration and spheroid formation, by downregulating NCAM1 via autocrine and paracrine signaling of miR-30a-5p. Inhibiting the miR-30a-5p/NCAM1 axis reverses the tumor-promoting effects of acrolein treatment. Analysis of tumor samples from GL261 tumor–bearing mice and patients with glioma showed that decreased NCAM1 levels in glioma tissues correlate with elevated acrolein expression. In samples of patients with GBM, lower NCAM1 levels are associated with a worse prognosis. This study suggests that targeting the miR-30a-5p/NCAM1 axis could be a potential therapeutic strategy for GBM.

Supplementary Figure 11. Exosomal miR-30a-5p in serum samples of glioma patients compared to healthy donors.

Supplementary Figure 5. Regulatory mechanisms of NCAM1 in a patient-derived GBM cell line, W2144.

Supplementary Table 5. Patient demographics and clinical characteristics of glioblastoma (GBM) patients.