miR-140-5p alleviates the aggressive progression of Wilms’ tumor through directly targeting TGFBR1 gene

Abstract

Hailei Wang,1 Chunyan Lou,1 Na Ma2 1Department of Pediatrics, Huaihe Hospital of Henan University, Kaifeng, Henan, China; 2Department of Neurology, Henan Kaifeng Children’s Hospital, Kaifeng, Henan, China Background and objective: Although many miRNAs are identified to be deregulated and play vital roles in the progression of Wilms’ tumor (WT), there are still a large number of miRNAs are waiting for us to explore. The purpose of the present study is to investigate the different expressing profiles of miRNAs in WT tissues and the adjacent normal tissues, and probe the effects and mechanism of a certain miRNA among the different expressing miRNAs. Methods: miRNA microarray was recruited to assess the differently expressed miRNAs in WT tissues and normal tissues, which was further verified by RT-PCR. Receiver operating characteristic curves were performed to calculate the specificity and sensitivity of miRNAs in the diagnose of WT. CCK-8, flow cytometry, wound healing, transwell chamber and tumor-burdened assays were used to assess cell growth, apoptosis, migration, invasion and tumorigenesis. Luciferase report assay was used to evaluate the interaction between miR-140-5p and TGFBR1.Results: A total of 34 miRNAs were abnormally expressed in the WT tissues, among which, miR-140-5p was identified to be obviously down-regulated in WT tissues, and the AUC of it was 0.961. Besides, we found that patients with miR-140-5p low expression always had a shorter overall survival and more aggressive clinical features, such as bigger tumor size (P=0.002), higher pathological stage (P=0.003) and higher occurrence rate of lymph node metastasis (P=0.009) than those in patients with miR-140-5p high expression. Moreover, luciferase reporter assay showed that TGFBR1 was the direct target of miR-140-5p, which was negatively regulated by miR-140-5p and was highly expressed in WT tissues. Furthermore, knockdown of miR-140-5p obviously enhanced the proliferation and tumorigenesis and repressed the apoptosis of G401 cells, and these effects were all abolished when TGFBR1 was down-regulated. Conclusion: The present study illustrates that miR-140-5p functions as a tumor suppressor in the occurrence and development of WT via targeting TGFBR1, which provides theoretical foundation for serving miR-140-5p as a new diagnosis marker even a therapeutic target for WT. Keywords: miR-140-5p, TGFBR1, Wilms’ tumor  

Keywords

• miR-140-5p
• TGFBR1
• Wilms tumor