MicroRNA-126 Inhibits Proliferation, Migration, Invasion, and EMT in Osteosarcoma by Targeting ZEB1.

Abstract

Osteosarcoma (OS) is a tumor with rapid progression, high metastatic potential and poor clinical prognosis. This study was aimed to investigate the function of miR-126 in OS cells. The miR-126 expression in OS cell lines and OS tissues were explored by qRT-PCR. Then, the effects of miR-126 on proliferation, cycle, migration, invasion, and transforming growth factor (TGF)-β1 induced epithelial to mesenchymal transition (EMT) were assessed. Predicted by TargetScan, one of target genes for miR-126 was verified by luciferase activity assay. Meantime, the mRNA and protein expressions of ZEB1 were assessed by qRT-PCR and Western blot assay. Subsequently, the effect of ZEB1 silence on miR-126 down-regulated cells was also evaluated. Finally, the expressions of key kinases involved in c-Jun N-terminal kinase (JNK) and Janus-activated kinase (JAK)-1/signal transducer and activator of transcription (STAT)-3 pathways were detected by Western blot analysis. Result showed that miR-126 was down-regulated in OS tissues and cell lines. Overexpression of miR-126 significantly inhibited cell proliferation, migration, invasion, and TGF-β1 induced EMT. The effect of miR-126 knockdown was just the opposite. ZEB1 was predicted and verified as a target gene of miR-126. Meantime, the influence of miR-126 knockdown was abrogated by ZEB1 silence. Additionally, the phosphorylation levels of c-Jun, JNK, JAK1, and STAT3 were down-regulated in miR-126 over-expressed cells, and the effect of miR-126 knockdown was reversed by ZEB1 silence. In conclusion, miR-126 inhibits proliferation, migration, invasion and EMT in OS by targeting ZEB1 through inactivation of JNK and JAK1/STAT3 pathways. J. Cell. Biochem. 118: 3765-3774, 2017. © 2017 Wiley Periodicals, Inc.