VMP1, a novel prognostic biomarker, contributes to glioma development by regulating autophagy.
J Neuroinflammation
; 18(1): 165, 2021 Jul 26.
Article
em En
| MEDLINE
| ID: mdl-34311746
ABSTRACT
BACKGROUND:
Malignant 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.METHODS:
The 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.RESULTS:
VMP1 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.CONCLUSIONS:
Our 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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autofagia
/
Glioma
/
Proteínas de Membrana
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Neuroinflammation
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China