AUTHOR=Yang Jiankai , Sun Guozhu , Hu Yuhua , Yang Jipeng , Shi Yijun , Liu Hongjiang , Li Chen , Wang Yuanyu , Lv Zhongqiang , Niu Jianxing , Liu Honglei , Shi Xuefang , Wang Haiping , Li Pan , Jiao Baohua 

TITLE=Extracellular Vesicle lncRNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 Released From Glioma Stem Cells Modulates the Inflammatory Response of Microglia After Lipopolysaccharide Stimulation Through Regulating miR-129-5p/High Mobility Group Box-1 Protein Axis

JOURNAL=Frontiers in Immunology

VOLUME=Volume 10 - 2019

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.03161

DOI=10.3389/fimmu.2019.03161

ISSN=1664-3224

ABSTRACT=Glioma stem cells (GSCs) derived extracellular vesicles (EVs) can mediate the communication between GSCs and microglia. MALAT1 expression in GSCs, EVs, and the supernatant was detected by real-time PCR. The direct targeting between MALAT1 and miR-129-5p, miR-129-5p and HMGB1 were tested with luciferase reporter analysis. The expression and secretion of interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α were determined in lipopolysaccharide-stimulated microglia or miR-129-5p inhibitor transferred microglia exposing to GSCs EVs or EVs derived from siMALAT1 pre-transferred GSCs. MALAT1 was enriched in GSCs EVs compared with GSCs and up-regulated MALAT1 was also observed in microglia upon GSCs EVs incubation. The relative expression and secretion of IL-6, IL-8, and TNF-α in lipopolysaccharide-stimulated microglia were up-regulated in GSCs supernatant group, which could be reversed by DMA (EVs secretion inhibitor) co-administration or si-MALAT1 pre-transfection of GSCs. Luciferase reporter assay testified the direct binding of MALAT1 and miR-129-5p, miR-129-5p and HMGB1, and si-MALAT1 could up-regulate miR-129-5p expression and down-regulate HMGB1 expression in microglia cells. The concentration of IL-6, IL-8, and TNF-α in lipopolysaccharide-stimulated microglia exposing to EVs from siMALAT1 transfected GSCs could be up-regulated by miR-129-5p inhibition. EVs lncRNA MALAT1 released from GSCs could modulate the inflammatory response of microglia after lipopolysaccharide stimulation through regulating miR-129-5p/HMGB1 axis.