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Cancer Manag Res. 2019 Mar 11;11:2015-2025. doi: 10.2147/CMAR.S191249. eCollection 2019.

CIRP regulates BEV-induced cell migration in gliomas.

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Department of Neurosurgery, The Fourth Medical Centre of Chinese PLA General Hospital, Beijing 100048, China,
Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Beijing 100850, China,
Experimental Hematology and Biochemistry Lab, Beijing Institute of Radiation Medicine, Beijing 100850, China.
South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou 510005, China.
State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.



A better understanding of the underlying molecular mechanisms in treatment failure of bevacizumab (BEV) for malignant glioma would contribute to overcome therapeutic resistance.


Here, we used a quantitative proteomic method to identify molecular signatures of glioblastoma cell after BEV treatment by two-dimensional liquid chromatography-tandem mass spectrometry analysis and 6-plex iTRAQ quantification. Next, the function of cold-inducible RNA-binding protein (CIRP), one of the most significantly affected proteins by drug treatment, was evaluated in drug resistance of glioma cells by invasion assays and animal xenograft assays. Target molecules bound by CIRP were determined using RNA-binding protein immunoprecipitation and microarray analysis. Then, these mRNAs were identified by quantitative real-time PCR.


Eighty-seven proteins were identified with significant fold changes. The biological functional analysis indicated that most of the proteins were involved in the process of cellular signal transduction, cell adhesion, and protein transport. The expression of CIRP greatly decreased after BEV treatment, and ectopic expression of CIRP abolished cell migration in BEV-treated glioma cells. In addition, CIRP could bind mRNA of CXCL12 and inhibit BEV-induced increase of CXCL12 in glioma cells.


These data suggested that CIRP may take part in BEV-induced migration of gliomas by binding of migration-relative RNAs.


CXCL12; RNA binding; proteomics; therapeutic resistance

Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

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