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Overexpression of long noncoding RNA, NEAT1 promotes cell proliferation, invasion and migration in endometrial endometrioid adenocarcinoma

机译:长表达非编码RNA,NEAT1促进子宫内膜子宫内膜样腺癌中的细胞增殖,侵袭和迁移

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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(0)/G(1) arrest and also induced cell apoptosis in HEC-59 cells. Tumor metastasis real-time PRC array showed that six metastasisrelated 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. (C) 2016 Elsevier Masson SAS. All rights reserved.
机译:长的非编码RNA(lncRNA)在生物学过程和肿瘤发生过程中作为重要的调节剂出现。但是,尚不清楚lncRNA是否参与子宫内膜子宫内膜样腺癌(EEC)。在本研究中,我们探讨了富核转录本1(NEAT1)在EEC中的表达模式,临床意义和生物学功能。在EEC组织和细胞系中NEAT1的表达水平升高,而NEAT1的较高表达水平与FIGO分期和淋巴结转移呈正相关。 pGCMV-NEAT1转染的HEC-59细胞中NEAT1的过表达促进细胞生长,集落形成能力以及侵袭和迁移能力; siNEAT1转染敲除HEC-59细胞中NEAT1的效果相反。流式细胞仪分析表明,NEAT1的过表达导致S期细胞增加和细胞凋亡减弱,而NEAT1的敲低诱导G(0)/ G(1)阻滞并诱导HEC-59细胞凋亡。肿瘤转移实时PRC阵列显示六个与转移相关的基因(c-myc,胰岛素样生长因子1(IGF1),基质金属肽酶2(MMP-2)和基质金属肽酶7(MMP-7)被上调,而钙黏着蛋白NEAT1过表达的HEC-59细胞中的1和TIMP金属肽酶抑制剂2被下调)。进一步的qRT-PCR和Western印迹结果证实NEAT1调节c-myc,IFG1,MMP-2和MMP-7。总之,我们的数据强调了NEAT1在EEC发育中的重要性,而NEAT1可能是EEC的潜在治疗靶标。 (C)2016 Elsevier Masson SAS。版权所有。

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