MicroRNA-10b mediates TGF-β1-regulated glioblastoma proliferation, migration and epithelial-mesenchymal transition

Although it is well known that exaggerated proliferation, metastasis and the mesenchymal subtype is related with worst prognoses in glioblastoma (GBM) and that transforming growth factor-beta 1 (TGF-beta 1) is a potent factor in regulating the proliferation, migration and epithelial-mesenchymal transition (EMT) phenotype of GBM, the detailed mechanisms are still far from elucidated. MicroRNAs (miRNAs) are small non coding RNAs which play critical roles in various diseases by regulating target gene expression. We report that miR-10b, a molecule downstream of TGF-beta 1, is involved in TGF-beta 1-regulated GBM cell proliferation, migration and EMT. We found that exposure of GBM cells to TGF-beta 1 significantly upregulated miR-10b expression. Overexpression of miR-10b promotes GBM cell proliferation, migration and EMT, whereas depletion of miR-10b obtained reverse effects. Further studies uncovered that some tumor-associated genes including epithelial cadherin (E-cadherin), apoptotic protease activating factor 1 (Apaf-1) and phosphatase and tensin homolog (PTEN) are target genes of miR-10b. In human GBM xenografts, antagomiR directed against miR-10b markedly suppressed tumor growth, and the tumor volume shrunk from 1252.5 +/- 285 to 873.4 +/- 205 mm(3) after antagomiR-10b treatment for 3 weeks compared with the control group (P<0.01). Taken together, our data collectively demonstrate that the proliferation, migration and EMT features of GBM cells can be regulated by TGF-beta 1 stimulation through controlling miR-10b. Thus, our findings provide a rationale for targeting TGF-beta 1 or miR-10b for the treatment of GBM.