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Neurochemical Research

, Volume 45, Issue 2, pp 508–518 | Cite as

Activation of BDNF-AS/ADAR/p53 Positive Feedback Loop Inhibits Glioblastoma Cell Proliferation

  • Xinwen Lv
  • Chunyan Gu
  • Shiwen GuoEmail author
Original Paper

Abstract

Despite progress in conventional treatment for glioblastoma (GBM), the prognosis remains poor due to high tumor recurrence. Therefore, identification of new molecular mechanisms is a pressing need for betterment of GBM patient outcomes. qRT-PCR was used to determine BDNF-AS expression in GBM cells. CCK-8, EdU incorporation, and caspase-3 activity assays were employed to analyze biological functions of BDNF-AS. RIP and RNA pull-down were conducted to detect the interactions among BDNF-AS, ADAR, and p53. Actinomycin D was utilized to examine the stability of p53 mRNA. ChIP and luciferase reporter assays were performed to detect transcriptional activation of BDNF-AS by p53. We found that BDNF-AS was significantly downregulated in GBM cell lines, and its overexpression inhibited GBM cell growth, and promoted apoptosis. Importantly, we illustrated that BDNF-AS coupled with ADAR protein to potentiate stability of p53 mRNA and thus upregulate p53. Interestingly, we further identified p53 as a transcription factor of BDNF-AS, activating transcription of BNDF-AS. This study firstly demonstrated that BDNF-AS acted as a tumor suppressor in GBM and the positive feedback circuit of BDNF-AS/ADAR/p53 served an important mechanism to control GBM proliferation. Targeting this auto-regulatory loop may provide a potential therapeutic strategy for GBM patients.

Keywords

Glioblastoma BDNF-AS ADAR p53 Positive feedback loop 

Notes

Acknowledgements

The authors have a deep gratitude towards all lab members.

Compliance with Ethical Standards

Conflict of interest

The authors declared that they have no conflict of interest.

Supplementary material

11064_2019_2943_MOESM1_ESM.docx (442 kb)
Supplementary file1 (DOCX 442 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Department of NeurosurgeryThe First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina
  2. 2.Department of NeurosurgeryBaoji Centre Hospital of Shaanxi ProvinceBaojiChina
  3. 3.Yan’an University Affiliated HospitalYan’anChina

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