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24 February 2019 : Laboratory Research  

miR-483-5p Targets MKNK1 to Suppress Wilms’ Tumor Cell Proliferation and Apoptosis In Vitro and In Vivo

Kai Liu1ABEF, Bingsen He1ABEF, Jiang Xu1ABEF, Yang Li1ABEF, Cheng Guo1CD, Qinhui Cai1CD, Shuya Wang2G*

DOI: 10.12659/MSM.913005

Med Sci Monit 2019; 25:1459-1468

Abstract

BACKGROUND: Wilms’ tumor (WT) is the most common type of renal tumor in children and it has high mortality rates. MicroRNAs (miRNAs) are important regulators of cellular differentiation processes that have been discovered to contribute to the development of various kinds of tumors.

MATERIAL AND METHODS: The Wilms’ tumor tissues and adjacent tissues were obtained from 28 patients to quantity miR-483-5p expression level. The miR-483-5p mimics and scrambles were transfected into the human kidney WT cell line GHINK-1 to evaluate the effect of miR-483-5p on Wilms’ tumor cell proliferation and apoptosis in vitro. A total of 18 female BALB/c nu/nu mice were used to further confirm how miR-483-5p affects Wilms’ tumor in vivo.

RESULTS: In the present study, miR-483-5p was identified to be downregulated in Wilms’ tumor tissues compared with the normal adjacent tissues. Additionally, low expression of mir-483-5p was significantly correlated with unfavorable histology subtypes, lymphatic metastasis, and late clinical stage (stage III and IV). Overexpression of miR-483-5p inhibited the proliferation and colony formation of GHINK-1 (Wilms’ tumor) cells compared with the control group due to enhanced cell apoptosis. Furthermore, miR-483-5p upregulated the protein expression level of caspase-3. Finally, MAP kinase-interacting serine/threonine-protein kinase 1 was identified as a direct target of miR-483-5p, which was confirmed by luciferase reporter assay and Western blotting.

CONCLUSIONS: miR-483-5p suppressed WT cell proliferation via inducing apoptosis through targeting MKNK1. This may provide novel insights into the mechanisms underlying WT and a potential therapeutic candidate for the treatment of WT in the future.

Keywords: Genes, Wilms Tumor, Intracellular Signaling Peptides and Proteins, Kidney Neoplasms, Mice, Inbred BALB C, Middle Aged, Protein Serine-Threonine Kinases, transcriptome, Up-Regulation, Wilms Tumor

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750