MicroRNA-154 functions as a tumor suppressor and directly targets HMGA2 in human non-small cell lung cancer.

ABSTRACT

MicroRNA-154 (miR-154) is dysregulated in some human malignancies and is correlated with tumor progression. However, its expression and function in non-small cell lung cancer (NSCLC) remain unclear. Therefore, we explored the effects of miR-154 on NSCLC tumorigenesis and development. Using quantitative reverse transcription-polymerase chain reaction, we detected miR-154 expression in NSCLC cell lines and primary tumor tissues. The association between miR-154 expression and clinicopathological factors was investigated, and the effects of miR-154 on the biological behavior of NSCLC cells were examined. Ultimately, the potential regulatory effect of miR-154 on high-mobility group A2 protein (HMGA2) expression was confirmed. miR-154 was significantly downregulated in NSCLC cell lines and clinical specimens. Reduced miR-154 expression was significantly associated with lymph node metastasis, advanced TNM stage, and shorter overall survival. Multivariate regression analysis confirmed that downregulation of miR-154 was an independent unfavorable prognostic factor for patients with NSCLC. Overexpression of miR-154 inhibited NSCLC cell proliferation, invasion, and migration, and promoted cell apoptosis in vitro. Furthermore, a luciferase reporter assay identified HMGA2 as a direct target of miR-154. Our findings indicate that miR-154 may act as a tumor suppressor in NSCLC and would serve as a novel therapeutic agent for miR-based therapy.