VAMP8 facilitates cellular proliferation and temozolomide resistance in human glioma cells.

Abstract

Malignant glioma is a common and lethal primary brain tumor in adults. Here we identified a novel oncoprotein, vesicle-associated membrane protein 8 (VAMP8), and investigated its roles in tumorigenisis and chemoresistance in glioma. The expression of gene and protein were determined by quantitative PCR and Western blot, respectively. Histological analysis of 282 glioma samples and 12 normal controls was performed by Pearson's chi-squared test. Survival analysis was performed using the log-rank test and Cox proportional hazards regression. Cell proliferation and cytotoxicity assay were conducted using Cell Counting Kit-8. Autophagy was detected by confocal microscopy and Western blot. VAMP8 was significantly overexpressed in human glioma specimens and could become a potential novel prognostic and treatment-predictive marker for glioma patients. Overexpression of VAMP8 promoted cell proliferation in vitro and in vivo, whereas knockdown of VAMP8 attenuated glioma growth by arresting cell cycle in the G0/G1 phase. Moreover, VAMP8 contributed to temozolomide (TMZ) resistance by elevating the expression levels of autophagy proteins and the number of autophagosomes. Further inhibition of autophagy via siRNA-mediated knockdown of autophagy-related gene 5 (ATG5) or syntaxin 17 (STX17) reversed TMZ resistance in VAMP8-overexpressing cells, while silencing of VAMP8 impaired the autophagic flux and alleviated TMZ resistance in glioma cells. Our findings identified VAMP8 as a novel oncogene by promoting cell proliferation and therapeutic resistance in glioma. Targeting VAMP8 may serve as a potential therapeutic regimen for the treatment of glioma.