MicroRNA-145 inhibits migration and invasion by down-regulating FSCN1 in lung cancer

Background: The extraordinary invasive capability is a major cause of treatment failure and tumor recurrence in lung cancer. Evidence in other cell systems has implicated the regulatory role of microRNA-145 in cell motility and invasion, which promotes us to investigate the biological functions of miR-145 in lung cancer in this regard. Results: We have found that miR-145 is dramatically down-regulated in clinical specimen of lung cancer and is negatively correlated with the tumor pathological grading in the current study. The cells transfected by miR-145 expression vector have demonstrated retarded cell mobility. Using a bioinformatics analysis approach, fascin homolog 1 (FSCN1), actin-binding protein, has been identified as the target of miR-145. Over-expression of miR-145 mimics enhanced protein levels of E-cadherin and fibronectin, indicative of its inhibitory role in EMT occurrence. Mechanistic studies showed that miR-145 mimics inhibited FSCN1 expression and miR-145 inhibitor enhanced it. Over-expression of FSCN1 reversed miR-145-regulated expression of EMT markers, suggesting that FSCN1 mediated the inhibitory effects of miR-145. Our results revealed a novel mechanism that miR-145 inhibits lung cancer cells migration and invasion via FSCN1 downregulation. Conclusions: These results suggest that miR-145 may function as anti-migration and anti-invasion influence in lung cancer and provides a potential approach for developing miR-145-based therapeutic strategies for malignant lung cancer therapy.