MicroRNA-21 Promotes Glioma Cells Migration Via SOX2 Induced β-catenin Signaling

Background:Glioblastoma is the most common malignant brain tumor,and there is study identified that miRNA 21(miR-21) is massively elevated in nearly all analyzed human malignant gliomas specimens,and the miR-21 shows strong effect in promoting glioma invasion,while the mechanism underlying it is poorly understood.The researcher makes the high expression of miRNA-21 in glioma cells,then analysis of differential gene expression spectrum shows that SOX2 is over expression in glioma cells. Transcription factor SOX2 remains the pluripotency of stem cell,partici-pates in self-renew of cancer stem cell and plays important role during the initiation and development of various cancers. SOX2 is involved in the proliferation or initiation of several cancers such as glioblastoma,gastric and breast cancer. Overexpression of SOX2 promotes migration, invasion, and epithelial-mesenchymal transition through the Wnt/β-catenin pathway in laryngeal cancer Hep-2cells.β-catenin can induce cell malignant transformation and tumor progression through Wnt/Frizzled pathway.Objective: To observe the influence of migration when miR-21 、Sox2 、 β-catenin expression on glioma cells, discover regulation and mechanism.Methods: Different glioma cell line(U87, A172, T98, U343) were transfected with expression plasmid of miR-21,anti-miRNA-21,SOX2,SOX2-siRNA through liposome transfection, respectively. Glioma cells were treated with BIO or XVA-939.After transfection, we detect the migration of glioma cell lines by Transwell.Glioma cell line were transfected with expression plasmid of miR-21+ SOX2-siRNA; anti-miR21+expression plasmid of SOX2;miR-21+β-catenin-siRNA; anti-miR21+treat with BIO;SOX2+β-catenin-siRNA;BIO+SOX2-siRNA using Lipofectamine 2000,respectively. After transfection, we detect the migration of glioma cell lines by Transwell.Glioma cell line were transfected with expression plasmid of miR-21,miR-21-siRNA,expression plasmid of SOX2 and SOX2-siRNA using Lipofectamine 2000, respectively.we examined the effect of miR-21 and SOX2 on Wnt/β-catenin signaling by Flow cytometry.Results:Here we showed that the ectopic expression of miR-21 in glioma cells also elevated SOX2 expression, and the SOX2 siRNA eliminate the miR-21 enhanced glioma cells migration/invasion, and the independent SOX2 overexpression promote the glioma cellsmigration/invasion just alike the miR-21 ectopic expression. Further analysis shows that miR-21 also induced the enhancement of β-catenin signaling, it shows that the β-catenin signaling is an essential functional mediator of miR-21 promoted glioma cells migration/invasion. And theβ-catenin expression is depend on the SOX2, SOX2 siRNA dramatically reducing the β-catenin expression. Furthermore the specifically activateβ-catenin signaling with BIO is sufficient to restore glioma cells migration/invasion capacity that undermined by the SOX2 siRNA. Which indicating that β-catenin signaling is a function mediator that act at the downstream of SOX2.Conclution: The miR-21 enhance the glioma cells migration capacity via elevating the β-catenin signaling, while SOX2 is a functional mediator between the miR-21 and β-catenin signaling.