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PCBP2 Reduced Oxidative Stress-Induced Apoptosis in Glioma through cGAS/STING Pathway by METTL3-Mediated m6A
Xiang Chen1, Mingchuan Yu1, Wei Xu2
1Department of Rehabilitation Medicine, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang City, Jiangxi Province, China.
Purpose:
The most prevalent primary malignant tumor of CNS is glioma, which has a dismal prognosis. The theory of oxidative stress is one of the important theories in the study of its occurrence and development mechanism. In this study, the impacts of PCBP2 on glioma sufferers and the possible mechanisms were examined.
Methods:
Patients with glioma were obtained from May 2017 to July 2018. Quantitative PCR, microarray analysis, western blot analysis, and immunofluorescence were used in this experiment.
Results:
PCBP2 mRNA expression level and protein expression in patients with glioma were upregulated compared with paracancerous tissue. OS and DFS of PCBP2 low expression in patients with glioma were higher than those of PCBP2 high expression. PCBP2 promoted the progression and metastasis of glioma. PCBP2 reduced oxidative stress-induced apoptosis of glioma. PCBP2 suppressed the cGAS/STING pathway of glioma. PCBP2 protein interlinked with cGAS and cGAS was one target for PCBP2. METTL3-mediated m6A modification increases PCBP2 stability.
Conclusion:
Along the cGAS-STING signal pathway, PCBP2 decreased the apoptosis that oxidative stress-induced glioma caused, which might be a potential target to suppress oxidative stress-induced apoptosis of glioma.
Insights
High PCBP2 levels accelerate glioma progression and metastasis by reducing oxidative stress-induced apoptosis via the cGAS/STING pathway. Lower PCBP2 expression correlates with better outcomes in glioma patients.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Cellular Biology
Background:
- Glioma is a common and aggressive central nervous system (CNS) tumor with poor prognosis.
- Oxidative stress is implicated in glioma development and progression.
- Understanding molecular mechanisms is crucial for targeted therapies.
Purpose of the Study:
- To investigate the role of PCBP2 in glioma.
- To elucidate the underlying mechanisms of PCBP2's impact on glioma progression.
- To explore PCBP2 as a potential therapeutic target.
Main Methods:
- Quantitative PCR and microarray analysis for gene expression.
- Western blot and immunofluorescence for protein analysis.
- Analysis of patient data for overall survival (OS) and disease-free survival (DFS).
Main Results:
- PCBP2 mRNA and protein levels were significantly upregulated in glioma tissues.
- High PCBP2 expression was associated with shorter OS and DFS.
- PCBP2 promoted glioma progression and metastasis, suppressed oxidative stress-induced apoptosis, and inhibited the cGAS/STING pathway.
- PCBP2 directly interacted with cGAS, and its stability was enhanced by METTL3-mediated m6A modification.
Conclusions:
- PCBP2 plays a critical role in promoting glioma progression and metastasis.
- PCBP2 suppresses oxidative stress-induced apoptosis in glioma by inhibiting the cGAS/STING pathway.
- Targeting PCBP2 may offer a novel strategy to combat glioma and reduce oxidative stress-induced apoptosis.
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