MicroRNA-145 inhibits migration and invasion by down-regulating FSCN1 in lung cancer.
نویسندگان
چکیده
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.
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ورودعنوان ژورنال:
- International journal of clinical and experimental medicine
دوره 8 6 شماره
صفحات -
تاریخ انتشار 2015