MiR-32 functions as a tumor suppressor and directly targets SOX9 in human non-small cell lung cancer

Abstract

PurposeMicroRNA-32 (miR-32) is dysregulated in certain human malignancies and correlates with tumor progression. However, its expression and function in non-small cell lung cancer (NSCLC) remain unclear. Thus, the aim of this study was to explore the effects of miR-32 expression on NSCLC tumorigenesis and development.MethodsUsing real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR), we detected miR-32 expression in NSCLC cell lines and primary tumor tissues. The association of miR-32 expression with clinicopathological factors and prognosis was also analyzed. Then, the effects of miR-32 expression on the biological behavior of NSCLC cells were investigated. Finally, the potential regulatory effect of miR-32 on SOX9 expression was confirmed.ResultsmiR-32 expression levels were significantly downregulated in NSCLC compared with the corresponding noncancerous lung tissues (P<0.001). In addition, decreased miR-32 expression was significantly associated with lymph node metastasis (P=0.002), advanced tumor/nodes/metastasis (TNM) classification stages (P<0.001), and shorter overall survival (P<0.001). Multivariate regression analysis corroborated that downregulated miR-32 expression was an independent unfavorable prognostic factor for NSCLC patients. In vitro studies demonstrated that miR-32 overexpression reduced A549 cell proliferation, migration, and invasion, and promoted apoptosis. Furthermore, SOX9 was confirmed as a direct target of miR-32, using a luciferase reporter assay.ConclusionThese findings indicate that miR-32 may act as a tumor suppressor in NSCLC and could serve as a novel therapeutic agent for miR-based therapy.