Exosomal miR-214-5p Released from Glioblastoma Cells Modulates Inflammatory Response of Microglia after Lipopolysaccharide Stimulation through Targeting CXCR5

Author(s): Jian-kai Yang*, Hong-jiang Liu, Yuanyu Wang, Chen Li, Ji-peng Yang, Liang Yang, Xue-jiao Qi, Yin-long Zhao, Xue-fang Shi, Jing-chen Li, Guo-zhu Sun, Bao-hua Jiao.

Journal Name: CNS & Neurological Disorders - Drug Targets
(Formerly Current Drug Targets - CNS & Neurological Disorders)

Volume 18 , Issue 1 , 2019

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Graphical Abstract:


Abstract:

Background and Objective: Exosomes communicate inter-cellularly and miRNAs play critical roles in this scenario. MiR-214-5p was implicated in multiple tumors with diverse functions uncovered. However, whether miR-214-5p is mechanistically involved in glioblastoma, especially via exosomal pathway, is still elusive. Here we sought to comprehensively address the critical role of exosomal miR-214-5p in glioblastoma (GBM) microenvironment.

Methods: The relative expression of miR-214-5p was determined by real-time PCR. Cell viability and migration were measured by MTT and transwell chamber assays, respectively. The secretory cytokines were measured with ELISA kits. The regulatory effect of miR-214-5p on CXCR5 expression was interrogated by luciferase reporter assay. Protein level was analyzed by Western blot.

Results: We demonstrated that miR-214-5p was aberrantly overexpressed in GBM and associated with poorer clinical prognosis. High level of miR-214-5p significantly contributed to cell proliferation and migration. GBM-derived exosomal miR-214-5p promoted inflammatory response in primary microglia upon lipopolysaccharide challenge. We further identified CXCR5 as the direct target of miR-214- 5p in this setting.

Conclusion: Overexpression of miR-214-5p in GBM modulated the inflammatory response in microglia via exosomal transfer.

Keywords: miR-214-5p, glioblastoma, microglia, CXCR5, cytokine, brain tumor.

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Article Details

VOLUME: 18
ISSUE: 1
Year: 2019
Page: [78 - 87]
Pages: 10
DOI: 10.2174/1871527317666181105112009
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