Background and aims: microRNA-605 (miR-605) is dysregulated in multiple cancers and plays crucial roles in regulating cancer progression. However, little is known about the expression pattern and detailed roles of miR-605 in non-small-cell lung cancer (NSCLC). Thus, in this study, we evaluated miR-605 expression in NSCLC along with its clinical significance. More importantly, the detailed roles and the underlying molecular mechanisms of miR-605 in NSCLC were explored.
Material and methods: Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was employed to detect miR-605 expression in NSCLC tissues and cell lines. A series of experiments were performed to determine the effects of miR-605 upregulation on NSCLC cell proliferation, apoptosis, migration and invasion in vitro and tumor growth in vivo. In addition, the downstream regulatory mechanisms of miR‐605 action in NSCLC cells were explored.
Results: Decreased expression of miR-605 was frequently detected in NSCLC tissues and cell lines. Low expression of miR-605 was significantly correlated with the tumor size, TNM stage, and distane metastasis in NSCLC patients. Exogenous miR-605 expression inhibited proliferation, increased apoptosis, and inhibited metastasis of NSCLC cells in vitro. Additionally, miR-605 overexpression hindered the growth of NSCLC cells in vivo. Furthermore, Forkhead Box P1 (FOXP1) was identified as a direct target gene of miR-605 in NSCLC cells. Moreover, FOXP1 was highly expressed in NSCLC cells and showed an inverse correlation with miR-605 expression levels. Besides, silencing of FOXP1 simulated roles similar to miR-605 upregulation in NSCLC cells. FOXP1 reintroduction partially abolished the anticancer effects of miR-605 in NSCLC cells.
Conclusion: Our results revealed that miR-605 inhibited the oncogenicity of NSCLC cells in vitro and in vivo by directly targeting FOXP1, suggesting the importance of the miR-605/FOXP1 pathway in the malignant development of NSCLC.
Keywords: non-small-cell lung cancer, microRNA-605, proliferation, apoptosis, metastasis, Forkhead Box P1