Li Zhiguo, Wei Dianjun, Yang Chao, Sun Honggang, Lu Tao, Kuang Defeng
Department of Clinical Laboratory, The Second Hospital of Tianjin Medical University, Tianjin City, China.
Department of Clinical Laboratory, The First Affiliated Hospital of Xi'an Medical University, Xi'an City, Shaanxi Province, China.
Biomed Pharmacother. 2016 Dec;84:244-251. doi: 10.1016/j.biopha.2016.09.008. Epub 2016 Sep 21.
Long noncoding RNAs (lncRNAs) are emerging as important modulators in the biological processes and tumorigenesis. However, whether lncRNAs are involved in endometrial endometrioid adenocarcinoma (EEC) remains unclear. In the present study, we explored the expression pattern, clinical significance and biological function of nuclear enriched abundant transcript 1 (NEAT1) in EEC. The expression levels of NEAT1 were elevated in EEC tissues and cell lines, and higher expression levels of NEAT1 were positively correlated with FIGO stage and lymph node metastasis. Overexpression of NEAT1 in HEC-59 cells transfected with pGCMV-NEAT1 promotes cell growth, colony formation ability as well as invasive and migratory ability; while knock-down of NEAT1 in HEC-59 cells by siNEAT1 transfection exhibited the opposite effects. Flow cytometry analysis showed that overexpression of NEAT1 led to an increase in S-phase cells and attenuated cell apoptosis, and knock-down of NEAT1 induced G/G arrest and also induced cell apoptosis in HEC-59 cells. Tumor metastasis real-time PRC array showed that six metastasis-related genes (c-myc, insulin like growth factor 1(IGF1), matrix metallopeptidase 2 (MMP-2) and matrix metallopeptidase 7(MMP-7) were up-regulated, and Cadherin 1 and TIMP metallopeptidase inhibitor 2 were down-regulated) in NEAT1-overexpressing HEC-59 cells. Further qRT-PCR and western blot results confirmed that c-myc, IFG1, MMP-2 and MMP-7 were dys-regulated by NEAT1. Together, our data underscore the significance of NEAT1 in EEC development, and NEAT1 may a potential therapeutic target for EEC.
长链非编码RNA（lncRNAs）正逐渐成为生物过程和肿瘤发生中的重要调节因子。然而，lncRNAs是否参与子宫内膜样腺癌（EEC）尚不清楚。在本研究中，我们探讨了核富集丰富转录本1（NEAT1）在EEC中的表达模式、临床意义及生物学功能。NEAT1在EEC组织和细胞系中的表达水平升高，且NEAT1的高表达水平与国际妇产科联盟（FIGO）分期及淋巴结转移呈正相关。用pGCMV-NEAT1转染HEC-59细胞使NEAT1过表达可促进细胞生长、集落形成能力以及侵袭和迁移能力；而用siNEAT1转染HEC-59细胞敲低NEAT1则表现出相反的效果。流式细胞术分析表明，NEAT1过表达导致S期细胞增加并减弱细胞凋亡，而敲低NEAT1则诱导HEC-59细胞G0/G1期阻滞并诱导细胞凋亡。肿瘤转移实时PCR阵列显示，在NEAT1过表达的HEC-59细胞中，六个与转移相关的基因（c-myc、胰岛素样生长因子1（IGF1）、基质金属蛋白酶2（MMP-2）和基质金属蛋白酶7（MMP-7）上调，而钙黏蛋白1和金属蛋白酶组织抑制因子2下调）。进一步的qRT-PCR和蛋白质印迹结果证实，c-myc、IFG1、MMP-2和MMP-7受NEAT1调控异常。总之，我们的数据强调了NEAT1在EEC发生发展中的重要性，并且NEAT1可能是EEC的一个潜在治疗靶点。
