Ma Yu-Shui, Wu Ting-Miao, Lv Zhong-Wei, Lu Gai-Xia, Cong Xian-Ling, Xie Ru-Ting, Yang Hui-Qiong, Chang Zheng-Yan, Sun Ran, Chai Li, Cai Ming-Xiang, Zhong Xiao-Jun, Zhu Jian, Fu Da
Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, College of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
Oncotarget. 2017 Feb 14;8(7):11896-11905. doi: 10.18632/oncotarget.14435.
Increasing evidence supports that microRNA (miRNA) plays a significant functional role in cancer progression by directly regulating respective targets. In this study, the expression levels of miR-105-1 and its target gene were analyzed using genes microarray and hierarchical clustering analysis followed by validation with quantitative RT-PCR in hepatocellular carcinoma (HCC) and normal liver tissues. We examined the expression of nuclear receptor coactivator 1 (NCOA1), the potential target gene of miR-105-1, following the transfection of miR-105-1 mimics or inhibitors. Our results showed that miR-105-1 was downregulated in HCC tissues when compared with normal liver tissues and patients with lower miR-105-1 expression had shorter overall survival (OS) and progression free survival (PFS). Moreover, NCOA1 was confirmed to be a direct target of miR-105-1. Furthermore, concomitant high expression of NCOA1 and low expression of miR-105-1 correlated with a shorter median OS and PFS in HCC patients. In conclusion, our results provide the first evidence that NCOA1 is a direct target of miR-105-1 suggesting that NCOA1 and miR-105-1 may have potential prognostic value and may be useful as tumor biomarkers for the diagnosis of HCC patients.
越来越多的证据支持微小RNA(miRNA)通过直接调控各自的靶标在癌症进展中发挥重要的功能作用。在本研究中,运用基因芯片和层次聚类分析对miR-105-1及其靶基因的表达水平进行分析,随后在肝细胞癌(HCC)和正常肝组织中通过定量逆转录聚合酶链反应(RT-PCR)进行验证。在转染miR-105-1模拟物或抑制剂后,我们检测了miR-105-1潜在靶基因核受体辅激活因子1(NCOA1)的表达。我们的结果显示,与正常肝组织相比,miR-105-1在HCC组织中表达下调,且miR-105-1表达较低的患者总生存期(OS)和无进展生存期(PFS)较短。此外,NCOA1被证实是miR-105-1的直接靶标。而且,NCOA1高表达与miR-105-1低表达同时出现与HCC患者较短的中位OS和PFS相关。总之,我们的结果首次证明NCOA1是miR-105-1的直接靶标,提示NCOA1和miR-105-1可能具有潜在的预后价值,并且可能作为HCC患者诊断的肿瘤生物标志物。