MicroRNA-216b inhibits cell proliferation and invasion in glioma by directly targeting metadherin

Glioma is a well-known aggressive and malignant brain tumor, and accounts for similar to 30% of all brain and central nervous system tumors. A number of studies have indicated that the abnormal expression of specific microRNAs (miR) serves vital roles in the tumorigenesis and tumor development of human cancer, including glioma. miR-216b has been studied in a number of types of cancer. However, the expression pattern, molecular function and underlying mechanisms of miR-216b in glioma remain unclear. In the present study, it was demonstrated that the level of miR-216b was significantly decreased in glioma tissues and cell lines compared with matched normal tissues and primary normal human astrocytes. The reduced miR-216b expression level was correlated with the Karnofsky Performance Score and the World Health Organization grade of gliomas. Upregulation of miR-216b repressed cell proliferation and invasion in glioma. Additionally, metadherin (MTDH) was identified as a direct target gene of miR-216b in glioma. MTDH expression was demonstrated to be significantly upregulated and inversely associated with miR-216b expression in glioma specimens. MTDH knockdowns could simulate the cellular conditions induced by miR-216b overexpression in glioma cells. In addition, miR-216b regulated phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN/protein kinase B signaling pathways in glioma. These results suggested that miR-216b acted as a tumor suppressor in glioma by directly targeting MTDH and that the miR-216b/MTDH axis may be an effective therapeutic target for the treatment of patients with this disease.