|
编者按：浆细胞瘤变异易位1（PVT1）属于长链非编码核糖核酸（lncRNA），对于乳腺癌的发病机制具有重要作用。越来越多证据表明，PVT1基因座小分子核糖核酸（miRNA，miR）是PVT1致癌作用的主要驱动因素。不过，PVT1基因座miR-1204对于人类癌症的致癌作用和可能机制仍不明确。 2018年3月20日，英国《自然》旗下《癌基因》在线发表山东大学医学院、伯克利加利福尼亚大学劳伦斯伯克利国家实验室、山东大学齐鲁医院、山东大学海洋学院、南京中医药大学基础医学院、山东大学第二医院的研究报告，miR-1204通过维生素D受体（VDR）蛋白质编码基因促使乳腺癌细胞的上皮→间质转化和转移。 该研究发现miR-1204表达增加与乳腺癌预后不良相关。此外，miR-1204可以促使体外和体内乳腺癌细胞的增殖、上皮→间质转化和浸润。根据机制研究表明，miR-1204的靶基因为VDR。VDR抑制剂可以恢复miR-1204所致乳腺癌细胞增殖、肿瘤发生和转移。 因此，该研究结果表明，miR-1204通过VDR发挥乳腺癌致癌作用，针对该通路的靶向疗法，或可阻断乳腺癌的发生和发展。 Oncogene. 2018 Mar 20. [Epub ahead of print] miR-1204 targets VDR to promotes epithelial-mesenchymal transition and metastasis in breast cancer. Xiaoyan Liu, Lei Bi, Qin Wang, Mingxin Wen, Ce Li, Yidan Ren, Qinlian Jiao, Jian-Hua Mao, Chuanxin Wang, Guangwei Wei, Yunshan Wang. Shandong University School of Medicine, Jinan, Shandong, China; Lawrence Berkeley National Laboratory, Berkeley, CA, USA; Qilu Hospital, Shandong University, Jinan, China; Shandong University School of Ocean, Weihai, Shandong, China; School of Preclinical Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China; The Second Hospital of Shandong University, Jinan, Shandong, China. 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. DOI: 10.1038/s41388-018-0215-2
|
|
|
