LncRNA expression signatures of twist-induced epithelial-to-mesenchymal transition in MCF10A cells

LncRNA expression signatures of twist-induced epithelial-to-mesenchymal transition in MCF10A cells
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MCF10A细胞中扭转诱导的上皮间质转化的LncRNA表达特征

DOI:
10.1016/j.cellsig.2013.10.001
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发表时间:
2014-01-01
影响因子:
4.8
通讯作者:
Liu, Manran
Liu, Manran
中科院分区:
生物学2区
文献类型:
--
作者:
Hu, Ping;Yang, Jiajia;Liu, Manran

文献摘要

被引文献

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上皮 - 间质转化(EMT)与肿瘤转移相关。Twist是EMT的关键转录因子之一,与肿瘤细胞迁移有关。长链非编码RNA(lncRNAs)最近已成为参与广泛生物过程和复杂疾病的重要调控分子。然而,尚不清楚是否有信号网络和lncRNAs参与Twist诱导的EMT过程。以MCF10A/Twist为模型,利用lncRNA芯片和cDNA微阵列,在Twist诱导的EMT过程中,有超过99种lncRNAs和3164个基因受到调控。我们利用生物信息学分析(基因本体论、通路分析)和实验数据建立了一个与Twist诱导的EMT相关的下游信号网络。一系列经典信号通路(如WNT、MAPK、JAK/STAT、TGF - β、mTOR、Hedgehog和P53信号通路)以及几种lncRNAs[如lncRNA(chr6,26124411 - 26139312,+),lncRNA(chr1,41944445 - 41949874),lncRNA(chr17,44833874 - 44834830,+)]在MCF10A/Twist细胞中发生改变。更有趣的是,lncRNA(chr17,44833874 - 44834830,+),lncRNA(chr17,21142183 - 21156578),lncRNA(chr6,26124411 - 26139312,+)和lncRNA(chr19,438420 - 2083745)可能参与Twist诱导的EMT过程中WNT信号通路的调节或激活。在我们的研究中,这些发现首次确定Twist通过诱导lncRNAs和信号通路广泛的转录和功能变化促进侵袭和转移。(C)2013爱思唯尔公司。保留所有权利。
The epithelial-to-mesenchymal transient (EMT) is associated with tumor metastasis. Twist is one of the key transcription factors for EMT and relates to tumor cell migration. Long non-coding RNAs (lncRNAs) have recently emerged as important regulatory molecules involved in a broad range of biological processes and complicated diseases. However, it is unknown whether a signal network and IncRNAs are involved in Twist-induced EMT program. Taking MCF10A/rwist as a model, more than 99 IncRNAs and 3164 genes are regulated in the Twist-induced EMT process using lncRNA-array and cDNA micro-array. We establish a downstream signal network associated with EMT induced by Twist using bioinformatic analysis (Gene Ontology, pathway analysis) and experimental data. A set of multiple canonical signal pathways (such as WNT, MAPK, JAK/STAT, TGF-beta, mTOR, Hedgehog and P53 signaling pathways) and several lncRNAs [such as lncRNA (chr6, 26124411-26139312, +), lncRNA (chr1, 41944445-41949874,), lncRNA (chr17, 44833874-44834830, +)] are altered in MCF10A/Twist cells. More interestingly, lncRNA (chr17, 44833874-44834830, +), lncRNA (chr17, 2114218321156578,), lncRNA (chr6, 26124411-26139312, +) and lncRNA (chr19, 438420-2083745,) may be involved in regulation or activation of WNT signaling pathway in the Twist-induced EMT process. These findings first determine that Twist contributes to invasion and metastasis by inducing wide-ranging transcriptional and functional changes of lncRNAs and signal pathways in our study. (C) 2013 Elsevier Inc. All rights reserved.