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VMP1, a novel prognostic biomarker, contributes to glioma development by regulating autophagy

Authors
  • Lin, Wanzun1, 2, 3
  • Sun, Yun2, 3, 4
  • Qiu, Xianxin2, 3, 4
  • Huang, Qingting2, 3, 4
  • Kong, Lin1, 2, 3
  • Lu, Jiade J.2, 3, 4
  • 1 Fudan University Cancer Hospital, 4365 Kangxin Rd, Pudong, Shanghai, 201321, China , Shanghai (China)
  • 2 Shanghai Key Laboratory of Radiation Oncology (20dz2261000), Shanghai, 201321, China , Shanghai (China)
  • 3 Shanghai Engineering Research Center of Proton and Heavy Ion Radiation Therapy, Shanghai, 201321, China , Shanghai (China)
  • 4 Shanghai Proton and Heavy Ion Center, 4365 Kangxin Rd, Pudong, Shanghai, 201321, China , Shanghai (China)
Type
Published Article
Journal
Journal of Neuroinflammation
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Jul 26, 2021
Volume
18
Issue
1
Identifiers
DOI: 10.1186/s12974-021-02213-z
Source
Springer Nature
Keywords
Disciplines
  • Research
License
Green

Abstract

BackgroundMalignant glioma, especially glioblastoma, is a highly aggressive disease with a dismal prognosis. Vacuole membrane protein 1 (VMP1) is a critical autophagy-associated protein with roles in oncogenesis and tumor progression. However, the contribution of VMP1 to glioma development as well as its prognostic value has not been established.MethodsThe expression of VMP1 and clinicopathologic data for 1996 glioma samples were collected from authoritative public databases to explore its prognostic value. Lentiviral CRISPR-Cas9 gene editing system was performed to deplete VMP1 expression. Apoptosis assays, cell cycle assays, colony formation assays, and EdU incorporation analysis were conducted to validate the biological function of VMP1. Transmission electron microscopy was used to determine the role of VMP1 in regulating autophagy.ResultsVMP1 overexpression was associated with advanced disease and had a poor prognosis in patients with glioma. The depletion of VMP1 by CRISPR-Cas9 gene editing significantly inhibited cell proliferation, increased cell death, and induced cell cycle arrest. Mechanistically, VMP1 knockout blocked autophagic flux and thus sensitized glioma cells to radiotherapy and chemotherapy. Moreover, a nomogram model showed that VMP1 expression has high prognostic value for determining survival in glioma.ConclusionsOur results provide insights into the pathological and biological functions of VMP1, including its roles in promoting tumor growth and progression, and support its value as a new diagnostic and prognostic biomarker for glioma.

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