406908

MIR124-2

Transforming growth factor-alpha (TGF-alpha) is upregulated in advanced stages of prostate cancer and strongly correlated with metastasis. However, the effect of TGF-alpha on epithelial-mesenchymal transition (EMT) in prostate cancer and the underlying mechanisms remain unclear. Recently, microRNAs have emerged as new regulators of EMT. This study found that treatment of DU145 cells with TGF-alpha suppressed the expression of epithelial marker E-cadherin and increased the expression of mesenchymal marker Vimentin as well as changed the cell morphology from cobblestone shape to spindle shape. The level of miR-124 was downregulated by TGF-alpha in several different cancer cell lines. Enforced expression of miR-124 abolished TGF-alpha-induced EMT. Slug was proven to be a target of miR-124 and mediated the inhibitory effect of miR-124 on TGF-alpha-induced EMT. Furthermore, overexpression of miR-124 reduced the migratory and invasive capacity of TGF-alpha-treated DU145 cells. In conclusion, our findings suggest that miR-124 inhibits TGF-alpha-induced EMT in DU145 cells by targeting Slug. Thus, miR-124 may be a potential target for prostate cancer therapeutic intervention.

OBJECTIVES: Lung cancer remains the leading cause of cancer-related mortality worldwide. Recently, accumulating studies have evidenced that microRNAs (miRNAs) contribute to the carcinogenesis of lung cancer through acting as either oncogenes or tumor suppressors. The purpose of our study was to investigate the functional role of miR-124 in lung cancer. METHODS: The expression of miR-124 was assessed by real-time RT-PCR in non-small cell lung cancer (NSCLC) tissues in comparison to its adjacent normal tissues. After transfection with miR-124 Mimics or negative controls into A549 cells, migration and invasion assays, apoptosis, and cell viability were evaluated. Luciferase reporter assay and RT-PCR were performed to explore whether zinc finger e-box binding homeobox 1 (ZEB1) was a target of miR-124. Further, the effects of miR-124 Mimic on migration and invasion were assessed after overexpression of ZEB1. RESULTS: MiR-124 expression was significantly down-regulated in NSCLC tissues compared to the normal tissue. In in-vitro study, overexpression of miR-124 in A549 cells suppressed cell migration and invasion activity, decreased expression of vimentin, but increased expression of E-cadherin and induced apoptosis. Luciferase reporter assay ensured that ZEB1 was a direct target of miR-124 and was negatively regulated by miR-124. Overexpression of ZEB1 could reverse the effect of miR-124 Mimic on the migration and invasion of the cells. CONCLUSION: The results suggests that miR-124 inhibits lung cancer cell migration and invasion through suppressing epithelial-mesenchymal transition (EMT) and inducing apoptosis of the lung cancer cells.