Annals of translational medicine · 2020
Protective effect of c-Myc/Rab7a signal pathway in glioblastoma cells under hypoxia.
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Li Chenguang, Fang Yuanjian, Wang Kaikai, Gao Wei, Dou Zhangqi, Wang Xiaoyu, Zhang Sheng, Lenahan Cameron, Wu Xiaohua
Аннотация
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.
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.
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.