In recent years, increasing studies demonstrated that miR-145 plays a tumor suppressor role in many human cancers. In the present study, we evaluated the expression of miR-145 and A Disintegrin and Metalloproteinase 19 (ADAM19) in glioblastoma multiforme (GBM) tissues and cells. Furthermore, we investigated the mechanisms underlying miR-145/ADAM19-induced GBM biology. Here, we found that miR-145 expression was down-regulated, while ADAM19 expression was up-regulated in GBM tissues and cells. Moreover, miR-145 mimics repressed U87 and U251 cell proliferation, migration and invasion. miR-145 mimics also inhibited the epithelial-to-mesenchymal transition (EMT) of U87 and U251 cells. Mechanically, the 3′ untranslated region (3′-UTR) of ADAM19 mRNA was a direct target for miR-145. In addition, ADAM19 over-expression also partially abrogated miR-145-inhibited EMT. In conclusion, this work suggested that high miR-145 expression inhibited EMT of GBM cells by targeting ADAM19. Thus miR-145/ADAM19 can be suggested as a novel target for GBM patients.

Background/Aims: MiR-145 and Smad2 have been widely reported in the development and progression of human malignancies. In the present study, we investigated the correlation between miR-145 and Smad2 in human glioblastoma multiforme (GBM). Methods: The epithelial–mesenchymal transition (EMT) biomarkers and Smad2 were assessed by Western blot. The silencing of Smad2 was conducted by transfection of Smad2 siRNAs. The cell migration and invasion were evaluated using Transwell assays, respectively. The dual luciferase reporter assay was performed to identify whether Smad2 is a direct target of miR-145. Results: The epidermal growth factor (EGF) activated the phosphorylation of Smad2 in U87 and U251 cells in a time- and dose-dependent manner. However, treatment with silencing of Smad2 or overexpression of miR-145 significantly inhibited the expressions of total Smad2, N-cadherin, Vimentin and matrix metallopeptidase 9, but induced the expression of E-cadherin. In addition, silencing of Smad2 or overexpression of miR-145 also inhibited the migration and invasion of U87 and U251 cells. Mechanistically, Smad2 was confirmed to be a target gene of miR-145 by bioinformatics analysis and luciferase reporter assay. Restored Smad2 expression also reversed miR-145-induced inhibition of EMT in U87 and U251 cells. Conclusion: MiR-145 inhibits EGF-induced EMT via targeting Smad2 in human GBM. Therefore, miR-145 may be a promising biomarker and therapeutic target for GBM patients.

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