MicroRNA-539 inhibits the progression of Wilms’ Tumor through downregulation of JAG1 and Notch1/3

BACKGROUND: Previous studies demonstrated that miR-539 play an important role in the carcinogenesis of some cancers. The aim of the present study was to determine the role of miR-539 in the pathogenesis of Wilms' Tumor (WT). METHODS: The expression level of miR-539 was measured by qRT-PCR in 42 WT tissues and SK-NEP-1 cell line. Protein expression of genes (E-cadherin, N-cadherin, Vimentin, Notch 1, Notch 3 and JAG1) was assessed by Western blot. The function of miR-539 was investigated in SK-NEP-1 cells by MTT and Transwell assays. The relationship between miR-539 and JAG1 was verified by a dual luciferase assay in SK-NEP-1 cells. RESULTS: The expression level of miR-539 was significantly decreased in WT tissues. Downregulation of miR-539 was closely related to NWTS-5 stage, lymph node metastasis and histological type of WT patients. Furthermore, low miR-539 expression was associated with a shorter overall survival rate in WT patients. In vitro, overexpression of miR-539 suppressed proliferation, migration and invasion of SK-NEP-1 cells. In addition, JAG1 was a direct target of miR-539. MiR-539 inhibited the development of WT by inhibiting JAG1-Notch1/3 expressing and blocking EMT. CONCLUSION: MiR-539 inhibited the progression of WT through downregulation of JAG1 and Notch1/3.