microRNA-133b represses the progression of lung cancer through inhibiting SOX9/β-catenin signaling pathway

Abstract

MicroRNA-133b (miR-133b) has been shown to be down-regulated in lung cancer and functions as a tumor repressor. However, the underlying mechanisms of miR-133b in lung cancer are not clear. SOX9, a member of SOX family, serves as an oncogene in lung cancer by activating b-catenin signaling and was identified to be a direct target of miR-133b in breast cancer. Based on these data, the current study was performed to explore whether SOX9/b-catenin signaling is implicated in miR-133b-meditaed lung cancer repression. MiR-133b expression in lung cancer tissues and cells were detected by RT-PCR. CCK-8, colony formation, flow cytometry, transwell chamber and in vivo assays were carried out to determine cell proliferation, colony formation, apoptosis, cell cycle, invasion, and tumorigenesis. We found that miR-133b expression was decreased in lung cancer tissues and cells. Up-regulation of miR-133b reduced cell proliferation and colony formation, induced cell apoptosis and G0/G1 phase arrest, and decreased cell invasion. Besides, miR-133b up-regulation decreased the expression of b-catenin and SOX9. Cell viability inhibition and apoptosis promotion induced by miR-133b up-regulation were all impaired when SOX9 was up-regulated. Furthermore, miR-133b over-expression repressed the tumorigenesis of lung cancer cells with smaller tumor size and lower Ki-67 expression. Taken together, this study clarifies that miR-133b represses lung cancer progression by inhibiting SOX9/b-catenin signaling.