MiR-224 Promotes Lymphatic Metastasis by Targeting ANGPTL1 in Non-Small-Cell Lung Carcinoma

Background: MicroRNAs can regulates tumor metastasis either as an oncomiR or suppressor miRNA. Here, we investigate the role of miR-224 in lymphatic metastasis of non-small-cell lung cancer (NSCLC). Methods: : The expression of miR-224 was demonstrated by a validation cohort of 156 lung cancer patients (77 cases with lymphatic metastasis) by q-PCR. In vitro and in vivo experiments were performed to study the malignant phenotype after upregulation and inhibition of miR-224 expression. Furthermore, the direct target genes of miR-224 were determined by a luciferase reporter assay. Results: : miR-224 was identified as a high expression miRNA in the tumor tissues with lymphatic metastasis) with an area under the receiver operating characteristic curve (AUC) of 0.57. Forced expression of miR-224 in H1299 cells promoted not only the cell viability, plate clone formation, migration and invasion in vitro, but also tumor growth and lung metastasis in vivo. Consistently, inhibition of miR-224 suppressed the malignant characters both in vitro and in vivo. Molecular mechanism research suggested that miR-422a targeted the ANGPTL1 as a novel tumor suppressor. Conclusions: : The present study demonstrates that miR-224 is a potential marker for the prediction of lymphatic metastasis of NSCLC. And application of miR-224 may help for prophylactic intervention of NSCLC in clinical practice.