miR-592 functions as a tumor suppressor in human non-small cell lung cancer by targeting SOX9

A growing body of evidence suggests that microRNA-592 (miR-592) may be involved in the initiation and progression of cancer by targeting various molecules in several human cancers. However, the function and underlying molecular mechanism of miR-592 in non-small cell lung cancer (NSCLC) remains unclear. In the present study, we found that miR-592 was significantly downregulated in NSCLC cell lines and tissues by real-time quantitative RT-PCR (qRT-PCR), and that lower miR-592 expression was negatively associated with advanced tumor/nodes/metastasis (TNM) classification stages (P<0.01) and lymph node metastasis (P<0.01). Function assay demonstrated that the miR-592 mimic reduced in vitro cell proliferation, colony formation, migration and invasion in A549 cells (a NSCLC-derived cell line), and inhibited in vivo tumor cell growth in xenografted nude mice. Furthermore, the gender determining region Y (SRY)-related high mobility group box 9 (SOX9) was confirmed as a direct target of miR-592, using luciferase reporter, qRT-PCR and western blot assays. Enforced overexpression of SOX9 effectively reversed the tumor suppressive functions of miR-592 on NSCLC proliferation, colony formation, migration and invasion. These findings suggested that miR-592 functions as tumor suppressor in NSCLC by suppressing the activity of SOX9, and that miR-592 might serve as a promising therapeutic target for NSCLC treatment.