Background
Glioblastoma multiforme (GBM) is the most common primary brain tumor, and is associated with a poor prognosis. Hypoxia is prevalent in the microenvironment of GBM, and promotes tumorigenesis and resistance to anticancer therapy. However, its mechanism remains incompletely understood.
Conclusions
Collectively, our results suggest that the c-Myc/Rab7a pathway protects GBM cells from hypoxic injury via regulation of apoptosis and autophagy, contributing to the growth of GBM.
Methods
We used immunohistochemistry, quantitative real-time PCR, and Western blots to assess c-Myc and Rab7a expression levels in 12 GBM specimens from a single institution. A luciferase reporter assay was conducted to confirmed whether Rab7a is transcriptionally regulated by c-Myc. To clarify the precise role of c-Myc/Rab7a on GBM cell proliferation, we did in vitro and in vivo analyses with lentivirus vectors. Cell viability was assessed using a cell counting kit-8 assay in the context of hypoxia. Autophagy was measured using transmission electron microscopy and Western blot, and apoptosis was measured using flow cytometry and Western blot.
Results
Gene and protein expression of c-Myc and Rab7a were significantly upregulated in GBM specimens. Moreover, c-Myc regulated Rab7a by specifically interacting with the Rab7a promoter. Furthermore, hypoxia activated the c-Myc/Rab7a pathway, which protects GBM cells from damage caused by hypoxia. Importantly, c-Myc/Rab7a inhibited apoptosis and induced autophagy in vitro and in vivo. Conclusions: Collectively, our results suggest that the c-Myc/Rab7a pathway protects GBM cells from hypoxic injury via regulation of apoptosis and autophagy, contributing to the growth of GBM.