VAMP8 facilitates cellular proliferation and temozolomide resistance in human glioma cells

As one of the most notorious of malignancies, glioblastoma multiforme (GBM), accounts for 45.2% of all malignant primary brain tumors.1 Despite aggressive surgery, radiation, and chemotherapy, the life expectancy of patients averages a mere 14 months after diagnosis.2 Soluble N-ethylmaleimide-sensitive factor (NSF) receptor (SNARE) is a superfamily of small proteins with more than 35 members in mammals, varying in size and primary structure.3 As an essential mechanism for cellular activities, SNARE has been observed in the progression of various tumors.4,5 Vesicle-associated membrane protein 8 (VAMP8) was first identified as an endosomal SNARE that participates in diverse biological functions including endosomal fusion,6–8 the exocytosis of GLUT4 and insulin,9,10 regulation of exocytosis in secretory cells,11 sequential granule-to-granule fusion,11 and autophagy.12,13 Nevertheless, nobody has reported its involvement in tumor progression. Temozolomide (TMZ) is the most commonly used chemotherapeutic drug in clinical trials for glioma. However, a large number of patients are resistant to TMZ, which greatly compromise the clinical treatment. Thus, research on TMZ resistance is of great importance for ameliorating the therapeutic efficacy and alleviating the suffering of patients. Autophagy is a dynamic process of protein degradation that is essential for survival, differentiation, development, and homeostasis.14 Despite evidence demonstrating the role of autophagy in modifying TMZ resistance in GBM,15–17 it remains incompletely understood, and clarification is needed. In this study, we first analyzed the expression and prognostic value of VAMP8 in The Cancer Genome Atlas (TCGA) and a cohort of 282 glioma patients, and then investigated its roles on tumorigenisis and TMZ resistance in glioma. Our findings revealed that the dysregulation of VAMP8 is a potential component of glioma pathogenesis and TMZ resistance, which might become a new therapeutic target for patients with glioma.