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Published on: December 13, 2019
CIRP regulates BEV-induced cell migration in gliomas
Yu-Xiao Liu1, Jun-Nian Zhou2,3,4, Ke-Hui Liu5
1Department of Neurosurgery, The Fourth Medical Centre of Chinese PLA General Hospital, Beijing 100048, China, zhangzw301@163.com.
Cold-inducible RNA-binding protein (CIRP) expression decreases with bevacizumab (BEV) treatment in glioma cells. Restoring CIRP inhibits migration by binding CXCL12 mRNA, suggesting a role in overcoming therapeutic resistance.
Area of Science:
- Oncology
- Molecular Biology
- Proteomics
Background:
- Malignant gliomas are aggressive brain tumors.
- Bevacizumab (BEV) is used to treat malignant glioma, but therapeutic resistance is common.
- Understanding molecular mechanisms of BEV resistance is crucial for improving treatment outcomes.
Purpose of the Study:
- To identify molecular signatures associated with bevacizumab (BEV) treatment failure in malignant glioma.
- To investigate the role of cold-inducible RNA-binding protein (CIRP) in glioma drug resistance and BEV treatment.
Main Methods:
- Quantitative proteomic analysis (2D LC-MS/MS, 6-plex iTRAQ) to identify protein expression changes after BEV treatment.
- Functional assays (invasion, xenograft) to assess CIRP's role in drug resistance.
- RNA-binding protein immunoprecipitation and microarray analysis to identify CIRP-bound mRNAs.
Main Results:
- Eighty-seven proteins showed significant fold changes post-BEV treatment, primarily involved in signal transduction, cell adhesion, and protein transport.
- CIRP expression decreased significantly after BEV treatment.
- Ectopic CIRP expression inhibited cell migration in BEV-treated glioma cells and reduced CXCL12 mRNA levels.
Conclusions:
- CIRP plays a role in bevacizumab (BEV)-induced migration of gliomas.
- CIRP may exert its function by binding migration-related RNAs, such as CXCL12.
- Targeting CIRP could be a potential strategy to overcome therapeutic resistance in glioma.
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