1. Academic Validation
  2. Protective effect of c-Myc/Rab7a signal pathway in glioblastoma cells under hypoxia

Protective effect of c-Myc/Rab7a signal pathway in glioblastoma cells under hypoxia

  • Ann Transl Med. 2020 Mar;8(6):283. doi: 10.21037/atm.2020.02.173.
Chenguang Li 1 Yuanjian Fang 1 Kaikai Wang 1 Wei Gao 1 Zhangqi Dou 1 Xiaoyu Wang 1 Sheng Zhang 2 Cameron Lenahan 3 4 Xiaohua Wu 1
Affiliations

Affiliations

  • 1 Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University, Hangzhou 310009, China.
  • 2 Department of Neurology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, China.
  • 3 Burrell College of Osteopathic Medicine, Las Cruces, NM, USA.
  • 4 Center for Neuroscience Research, School of Medicine, Loma Linda University, Loma Linda, CA, USA.
Abstract

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.

Keywords

Apoptosis; Rab7a; autophagy; c-Myc; hypoxia.

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