Inhibition of JMJD6 expression reduces the proliferation, migration and invasion of neuroglioma stem cells
Abstract:
Neuroglioma is the most common form of human primary malignant brain tumor, more and more studies recently showed only a small subpopulation of glioma cells which called glioma stem cells have true tumorigenic potential. Meanwhile, it was reported the overexpression of JMJD6 protein is closely involvement with the occurrence and development of multiple tumors, and JMJD6 is required for the differentiation of multiple organ, tissues and cells during embryogenesis. However, the influence of JMJD6 overexpression on neuroglioma development is unclear now. Hence, to explore the effects of JMJD6 expression on neuroglioma, we firstly isolated glioma stem cells by using CD133 MicroBead Kit, and identified via neurosphere-forming assay and Immunofluorescence staining. At the same time, we investigated the effects and mechanism of JMJD6 on the proliferation, migration and invasion of glioma stem cells through MTT, transwell assays and the Cignal finder cancer 10-pathway reporter array. The results demonstrated that the glioma neurosphere cells positively expressed stem cell marker SOX2, neuroectodermal stem cell marker Nestin, and also expressed astrocytes marker GFAP and neurons marker β-tubulin III fter FBS-induced differentiation for a week, which proved the glioma neurosphere cells have the self-renewal and multipotential differentiation capacity. Moreover, shRNA lentiviral vector mediated knockdown of JMJD6 in glioma stem cells led to decreased proliferation, migration and invasion, the underlying molecular mechanism is related to the weaken of Wnt signaling pathway and strengthen of p53 signaling pathway.