MIR-124 inhibits cell proliferation, migration and invasion by directly targeting SOX9 in lung adenocarcinoma

Abstract

Accumulating evidence indicates that dysregulation of microRNAs (miRNAs) may contribute to the initiation and progression of cancer. However, the role of MIR-124 in lung adenocarcinoma (ADC) and the underlying mechanisms through which MIR-124 exerts its functions are not completely understood. In the present study, we detected MIR-124 and SOX9 expression in lung ADC tissues. The results showed that MIR-124 was significantly downregulated in the lung ADC tissues compared with that noted in the corresponding non-cancerous lung tissues and the level of SOX9 protein was inversely associated with the expression of MIR-124. The study in human lung ADC cell line A549 demonstrated that upregulation of MIR-124 could inhibit cell proliferation, migration and invasion. The bioinformatic analysis showed that there was a putative MIR-124 binding site in the 3' untranslated region (3'UTR) of SOX9. Using a luciferase reporter assay, we verified that SOX9 is a direct target of MIR-124. Furthermore, overexpression of MIR-124 repressed SOX9 expression, whereas inhibition of MIR-124 increased expression of SOX9 in the A549 cells. Finally, we identified that SOX9 was a functional mediator of MIR-124 in A549 cells. Taken together, our results suggest that MIR-124 functions as a tumor suppressor in lung ADC by directly targeting SOX9 and it may be a promising candidate for MIR-based therapy against lung ADC.