Department of Pediatrics, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China (mainland).
Department of Rheumatology and Immune Disease, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China (mainland).
Med Sci Monit. 2019 Feb 24;25:1459-1468. doi: 10.12659/MSM.913005.
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.
Wilms 瘤（WT）是儿童中最常见的肾肿瘤类型，其死亡率较高。微小 RNA（miRNA）是细胞分化过程的重要调节因子，已发现其有助于各种肿瘤的发展。
从 28 名患者中获得 Wilms 肿瘤组织和相邻组织，以定量 miR-483-5p 的表达水平。将 miR-483-5p 模拟物和 scramble 转染到人肾 WT 细胞系 GHINK-1 中，以评估 miR-483-5p 对 Wilms 肿瘤细胞体外增殖和凋亡的影响。总共使用 18 只雌性 BALB/c nu/nu 小鼠进一步确认 miR-483-5p 如何影响体内 Wilms 肿瘤。
在本研究中，与正常相邻组织相比，Wilms 肿瘤组织中 miR-483-5p 被鉴定为下调。此外，mir-483-5p 表达水平低与不良组织学亚型、淋巴转移和晚期临床分期（III 和 IV 期）显著相关。与对照组相比，miR-483-5p 的过表达抑制了 GHINK-1（Wilms 肿瘤）细胞的增殖和集落形成，这是由于细胞凋亡增强所致。此外，miR-483-5p 上调了 caspase-3 的蛋白表达水平。最后，通过荧光素酶报告基因测定和 Western blot 证实，丝氨酸/苏氨酸蛋白激酶 1 是 miR-483-5p 的直接靶标。
miR-483-5p 通过靶向 MKNK1 诱导凋亡来抑制 WT 细胞增殖。这可能为 Wilms 瘤的发病机制提供新的见解，并为未来治疗 Wilms 瘤提供潜在的治疗候选物。
