Abstract
Glioma stem cell (GSC)–derived extracellular vesicles (EVs) can mediate the communication between GSCs and microglia. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) expression in GSCs, EVs, and 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 to microglia exposed to GSC EVs or EVs derived from siMALAT1 pre-transferred GSCs. MALAT1 was enriched in GSC EVs compared with GSCs, and up-regulated MALAT1 was also observed in microglia upon GSC EVs incubation. The relative expression and secretion of IL-6, IL-8, and TNF-α in lipopolysaccharide-stimulated microglia were up-regulated in the GSC supernatant group, which could be reversed by dimethyl amiloride (DMA) (EV 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 exposed 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 the miR-129-5p/HMGB1 axis.
Highlights
Originated from brain or spine glial cells, glioma may account for nearly 80% of malignant cerebral tumors
LncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) Correlates With miR-129-5p and high mobility group box-1 protein (HMGB1) Expression in glioma stem cells (GSCs)
Cell viability indicated by CCK-8 assay showed that si-MALAT1 could significantly suppress GSC growth when compared with the si-normal control (NC) group and control group (Figure 2B, P < 0.01)
Summary
Originated from brain or spine glial cells, glioma may account for nearly 80% of malignant cerebral tumors. According to the WHO Neuropathological Classification of Tumors of the Central Nervous System, glioma can be classified into lowgrade gliomas (WHO grade II) and high-grade (WHO grade III–IV). Macrophages and/or microglia may account for a considerable portion of glioma mass [4], and the number and intensity of the infiltrated microglia/macrophages are intimately correlated with the metastasis and progression of glioma. Substantial evidence indicates the indispensable role of the immunesuppressive milieu induced by the interaction between glioma and microglia/macrophages, which will eventually favor the growth, invasion, metastasis, and neoangiogenesis of glioma cell [5]. The precise functioning and underlying mechanism involved in the interaction of GSCs and tumor-infiltrated microglia are still to be addressed
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