Department of Human Anatomy and Key Laboratory of Experimental Teratology, Ministry of Education, Shandong University School of Medicine, 44 Wenhua Xi Road, Jinan, 250012, Shandong, China.
Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.
Oncogene. 2018 Jun;37(25):3426-3439. doi: 10.1038/s41388-018-0215-2. Epub 2018 Mar 20.
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.
浆细胞瘤变异易位 1（PVT1）是一种长链非编码 RNA，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，位于 PVT1 基因座的 miRNAs 是 PVT1 在癌症中致癌作用的主要驱动因素。然而，位于 PVT1 基因座的 miR-1204 在人类癌症中的致癌作用及其潜在机制尚不清楚。在这项研究中，我们发现 miR-1204 的表达增加与 BC 的预后不良有关。此外，miR-1204 促进了 BC 细胞在体外和体内的增殖、上皮-间充质转化和侵袭。机制研究表明，VDR 是 miR-1204 的一个新的靶基因。VDR 的干扰恢复了 miR-1204 介导的 BC 细胞增殖、致瘤性和转移。总之，我们的研究结果表明，miR-1204-VDR 通路在 BC 中发挥致癌作用，具有阻断 BC 发生和发展的潜在治疗应用。
