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

Abstract:

BACKGROUND: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. METHODS: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. RESULTS: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. CONCLUSION: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.

journal_name

Neuro Oncol

journal_title

Neuro-oncology

authors

Chen Y,Meng D,Wang H,Sun R,Wang D,Wang S,Fan J,Zhao Y,Wang J,Yang S,Huai C,Song X,Qin R,Xu T,Yun D,Hu L,Yang J,Zhang X,Chen H,Chen J,Chen H,Lu D

doi

10.1093/neuonc/nou219

subject

Has Abstract

pub_date

2015-03-01 00:00:00

pages

407-18

issue

3

eissn

1522-8517

issn

1523-5866

pii

nou219

journal_volume

17

pub_type

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