MiR-143 suppresses the epithelial-mesenchymal transition of spinal glioblastoma through down-regulation of ERK5.

The spinal glioblastoma (GBM) represents the one of most common tumors in humans. However, the biological processes and molecular mechanisms of spinal GBM are still unclear. It is known that miR-143 participates in the development of various tumor progressions. The present study was to evaluate the level of miR-143 in spinal GBM tissues and cells. We further investigated that the molecular mechanisms of miR-143 in U87 and U251 cell lines. Here, our data showed that the expression levels of miR-143 were significantly reduced in spinal GBM tissues and cell lines. Accordingly, the expression levels of the extracellular signal regulated kinase 5 (ERK5) were significantly increased in spinal GBM tissues and cell lines. Ectopic expression of miR-143 in U87 and U251 cells resulted in decreased cell growth and enhanced cell apoptosis, and inhibited the expression of epithelial-mesenchymal transition (EMT) biomarkers. Further study characterized the 3' untranslated region (3'-UTR) of ERK5 gene as a direct target of miR-143 in U87 and U251 cells as determined by luciferase reporter assays. In addition, the ectopic expression of miR-143 led to the down-regulation of epidermal growth factor receptor (EGFR), while the over-expression of ERK5 reversed the miR-143-inhibited EGFR expression, and promoted cell growth and the expression of EMT biomarkers. In conclusion, this study demonstrated that miR-143 plays a crucial role in regulating the EMT of GBM by directly targeting ERK5, and miR-143 may act as a potential therapeutic target in spinal GBM patients.