miR-1204 targets VDR to promotes epithelial-mesenchymal transition and metastasis in breast cancer
miR-1204 targets VDR to promotes epithelial-mesenchymal transition and metastasis in breast cancer
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miR-1204靶向VDR促进乳腺癌上皮间质转化和转移
DOI：
10.1038/s41388-018-0215-2
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发表时间：
2018-06-01
期刊：
影响因子：
8
通讯作者：
Wang, Yunshan
中科院分区：
文献类型：
--
作者：
Liu, Xiaoyan;Bi, Lei;Wang, Yunshan
浆细胞瘤变异易位 1 (PVT1) 是一种 lncRNA，在乳腺癌 (BC) 发病机制中发挥重要作用。越来越多的证据表明，PVT1 基因座中的 miRNA 是 PVT1 在癌症中致癌作用的主要驱动力。然而，位于PVT1位点的miR-1204在人类癌症中的致癌作用和潜在机制仍不清楚。在这项研究中，我们发现 miR-1204 表达增加与 BC 预后不良相关。此外，miR-1204 在体外和体内均可促进 BC 细胞的增殖、上皮间质转化和侵袭。机制研究表明VDR是miR-1204的新靶基因。 VDR 的干扰可恢复 miR-1204 介导的 BC 细胞增殖、肿瘤发生和转移。总的来说，我们的结果表明 miR-1204-VDR 通路在 BC 中发挥致癌作用，在阻止 BC 发生和进展方面具有潜在的治疗应用。
Plasmacytoma variant translocation 1 (PVT1) is an lncRNA that plays vital roles in breast cancer (BC) pathogenesis. Increasing evidence suggests that miRNAs that reside in the PVT1 locus are the main driver of the oncogenic roles of PVT1 in cancer. However, the oncogenic role and underlying mechanism of miR-1204, located in the PVT1 locus, in human cancer is still unclear. In this study, we discovered that increased expression of miR-1204 is associated with poor prognosis in BC. Moreover, miR-1204 promotes proliferation, epithelial-mesenchymal transition and invasion of BC cells both in vitro and in vivo. Mechanistic investigations demonstrated that VDR is a novel target gene of miR-1204. Interference of VDR restored miR-1204-mediated BC cell proliferation, tumorigenesis, and metastasis. Collectively, our results demonstrated that the miR-1204-VDR pathway exerts oncogenic effects in BC with potential therapeutic applications in blocking BC development and progression.