Role of miR-486-5p in regulating renal cell carcinoma cell proliferation and apoptosis via TGF-β-activated kinase 1
Role of miR-486-5p in regulating renal cell carcinoma cell proliferation and apoptosis via TGF-β-activated kinase 1
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DOI：
10.1002/jcb.26900
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发表时间：
2019-03-01
影响因子：
4
通讯作者：
Liu, Ying
中科院分区：
文献类型：
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作者：
He, Yanfa;Liu, Jianzhen;Liu, Ying
肾细胞癌(RCC)是成人常见的肾脏肿瘤。MiR-486-5p在肾癌中的作用尚不清楚。本研究的目的是寻找在肾癌中受miR-486-5p调控的新靶点，以更深入地了解该网络，并更好地了解这些microRNAs及其靶点在肾癌发生发展中的作用。我们进行了一系列测试，发现miR-486-5p在肾癌细胞中的表达水平一直较低。恢复肾癌细胞miR-486-5p的表达可抑制细胞增殖，增加细胞凋亡率。进一步研究表明，转化生长因子-β激活蛋白1是miR-486-5p在肾癌细胞中的靶基因。肿瘤相关巨噬细胞的C-C基序趋化因子配体2(CCL2)下调miR-486-5p的表达，抑制CCL2诱导的肾癌细胞增殖和抗凋亡作用。提示miR-486-5p在肾癌中具有潜在的诊断和治疗价值。
Renal cell carcinoma (RCC) is a common kidney tumor in adults. The role of miR-486-5p in RCC is unknown. The aim of our study was to identify new targets regulated by miR-486-5p in RCC, to obtain a deeper insight into the network and to better understand the role of these microRNAs and their targets in carcinogenesis of RCC. We performed a series of tests and found consistently lower expression levels of miR-486-5p in kidney cancer cells. Restoration of miR-486-5p expression in RCC cells could lead to the suppression of cell proliferation and the increase of cell apoptosis. Further studies demonstrated that TGF-beta-activated kinase 1 was a target gene of miR-486-5p in kidney cancer cells. It was also shown that C-C motif chemokine ligand 2 (CCL2) from tumor-associated macrophages downregulated miR-486-5p expression, and miR-486-5p inhibited RCC cell proliferation and apoptosis resistance induced by CCL2. The study demonstrates that there are potential diagnosis and therapy values of miR-486-5p in RCC.