MicroRNA-21 promotes migration and invasion of glioma cells via activation of Sox2 and β-catenin signaling

The expression of microRNA 21 (miR-21) has been reported to be upregulated in various types of cancer, including malignant gliomas. However, its functions and mechanisms in glioma remain to be fully elucidated. The present study established miRNA-21 overexpression and knockdown cell lines using SRY-box 2 (Sox2) small interfering RNA (siRNA) to knockdown expression and Sox2 cDNA was cloned into pcDNA 3.1 mammalian expression vector for ectopic expression. BIO and XAV-939 were used for β-catenin signaling activation and knockdown, respectively. Transwell chambers were used to assay the capacity of cells to migrate. The present study determined that increased expression of miR-21 significantly promoted the migration and invasion of glioma cells, which was accompanied by an upregulated expression of the Sox2 protein. Sox2 overexpression also promoted glioma cell migration and invasion, whereas Sox2 siRNA markedly reduced the miR-21-enhanced migration and invasion of glioma cells, indicating Sox2 may act as a crucial mediator of miR-21 function. Furthermore, miR-21 also upregulated the protein expression level of β-catenin, whereas anti-miR-21 and Sox2 knockdown significantly reduced β-catenin expression. BIO, a β-catenin specific agonist, enhanced migration and invasion of glioma cells. XAV-939, an inhibitor of β-catenin signaling, markedly inhibited the migration and invasion of glioma cells, suggesting that β-catenin may be associated with miR-21- and Sox2-induced invasion of glioma cells. Notably, BIO restored the migration and invasion potential of glioma cells, which were inhibited by Sox2 siRNA and anti-miR-21. These findings indicated that β-catenin may be an important downstream mediator of miR-21 and Sox2. Therefore, the present study identified the miR-21/Sox2/β-catenin signaling pathway, which may regulate the migration and invasion of human glioma cells.