miR-133a suppresses cell proliferation, migration and invasion in human lung cancer by targeting MMP-14

Lung cancer is the leading cause of cancer-related mortality worldwide. Over half of lung cancer cases are diagnosed after metastasis, for which the median survival time is approximately 8 months. microRNAs (miRNAs), which are a class of single-stranded endogenous non-coding RNAs, are likely to be involved in most biological processes. miR-133 plays roles in cardiac development and disease, and recent studies showed that miR-133 is downregulated in various human malignancies, such as bladder and lung cancer. However, its detailed role in the processes of cancer remains to be determined. In the present study, we found that in the lung cancer cell lines A549 and NCI-H1299 overexpression of miR-133a suppressed cell proliferation, migration and invasion. The miR-133a-induced suppression of cell migration and invasion can be reversed by miR-133a-specific inhibitor. According to the mRNA sequence, matrix metalloproteinase (MMP)-14, which is an important regulator of metastasis, is a predicted target of miR-133a. This was confirmed by dual luciferase reporter assay. Moreover, miR-133a overexpression decreases the mRNA and protein levels of MMP-14. Collectively, these results suggest that miR-133a may inhibit lung cancer metastasis by targeting MMP-14 and may be used as an anti-metastatic therapy in lung cancer patients.