MiRNA-203a-5p alleviates the malignant progression of Wilms' tumor via targeting JAG1.

ABSTRACT

OBJECTIVE: To uncover the potential influence of microRNA-203a-5p (miRNA-203a-5p) on the malignant progression of Wilms' tumor (WT). PATIENTS AND METHODS: MiRNA-203a-5p levels in 49 paired WT and paracancerous tissues were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Prognostic value of miRNA-203a-5p in WT was assessed by the Kaplan-Meier method. Correlation between miRNA-203a-5p level and clinical data of WT patients was analyzed. In G401 and SK-NEP-1 cells, in vitro functions of miRNA-203a-5p in regulating metastatic abilities were explored. The interaction between miRNA-203a-5p and JAG1, and their regulatory role in the malignant progression of WT were evaluated by Dual-Luciferase reporter gene assay and rescue experiments. RESULTS: MiRNA-203a-5p was downregulated in WT tissues than that of paracancerous ones. WT patients expressing low level of miRNA-203a-5p had higher risk of lymphatic metastasis and worse prognosis. Overexpression of miRNA-203a-5p attenuated migratory and invasive abilities in G401 cells. On the contrary, knockdown of miRNA-203a-5p yielded the opposite trends in SK-NEP-1 cells. JAG1 was verified to be the direct gene binding miRNA-203a-5p, which was negatively regulated by miRNA-203a-5p in WT cells. Rescue experiments finally uncovered that miRNA-203a-5p alleviated the malignant progression of WT via negatively regulating JAG1. CONCLUSIONS: MiRNA-203a-5p is downregulated in WT and closely linked to lymphatic metastasis of WT patients. By negatively regulating JAG1, miRNA-203a-5p alleviates the malignant progression of WT.