Prediction of long noncoding RNA functions with co-expression network in esophageal squamous cell carcinoma.

Prediction of long noncoding RNA functions with co-expression network in esophageal squamous cell carcinoma.
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DOI:
10.1186/s12885-015-1179-z
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发表时间:
2015-03-24
期刊:
影响因子:
3.8
通讯作者:
Cao W
Cao W
中科院分区:
医学2区
文献类型:
--
作者:
Hao Y;Wu W;Shi F;Dalmolin RJ;Yan M;Tian F;Chen X;Chen G;Cao W

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长链非编码RNA(lncRNA)在基因组中广泛转录。它们在染色质重塑和基因表达中具有重要的调节功能。已在癌症中研究了失调的lncRNA,但其在食管鳞状细胞癌(ESCC)中的作用在很大程度上仍然未知。我们对4例食管鳞癌患者的原发癌组织和癌旁正常组织进行了lncRNA的表达筛选和全基因组lncRNA及其编码基因的表达分析,结合实验和生物信息学方法,试图了解lncRNA在食管癌发生中的作用。LncRNA阵列用于编码和非编码RNA表达。R程序和Bioconductor软件包(limma和RedeR)用于差异表达和共表达网络分析,随后通过定量真实的时间聚合酶链反应、小干扰RNA介导的敲低、凋亡和体外侵袭试验对推测的癌-lncRNA ESCCAL-1进行独立确认和功能研究。整体编码和lncRNA基因表达模式能够将ESCC与邻近正常组织区分开。构建了食管鳞癌差异表达的编码基因和lncRNA基因的共表达网络,并据此推测lncRNA的功能。LncRNA ESCCAL-1是预测的新型癌-lncRNA的一个例子,它在65%的独立ESCC患者队列中过表达(n = 26)。此外,ESCCAL-1表达的敲低增加了食管癌细胞的凋亡,并降低了体外侵袭。我们的研究揭示了ESCC相关lncRNA的景观。通过对lncRNA编码网络和共表达网络的系统分析,加深了对lncRNA在生物网络中的理解。ESCCAL-1是食管癌发生发展中的一种新的推定癌基因lncRNA。本文的在线版本(doi:10.1186/s12885-015-1179-z)包含补充材料,可供授权用户使用。
Long non-coding RNAs (lncRNAs) are pervasively transcribed in the genome. They have important regulatory functions in chromatin remodeling and gene expression. Dysregulated lncRNAs have been studied in cancers, but their role in esophageal squamous cell carcinoma (ESCC) remains largely unknown. We have conducted lncRNA expression screening and a genome-wide analysis of lncRNA and coding gene expression on primary tumor and adjacent normal tissue from four ESCC patients, tend to understand the functionality of lncRNAs in carcinogenesis of esopheagus in combination with experimental and bioinformatics approach. LncRNA array was used for coding and non-coding RNA expression. R program and Bioconductor packages (limma and RedeR) were used for differential expression and co-expression network analysis, followed by independent confirmation and functional studies of inferred onco-lncRNA ESCCAL-1 using quantitative real time polymerase chain reaction, small interfering RNA-mediated knockdown, apoptosis and invasion assays in vitro. The global coding and lncRNA gene expression pattern is able to distinguish ESCC from adjacent normal tissue. The co-expression network from differentially expressed coding and lncRNA genes in ESCC was constructed, and the lncRNA function may be inferred from the co-expression network. LncRNA ESCCAL-1 is such an example as a predicted novel onco-lncRNA, and it is overexpressed in 65% of an independent ESCC patient cohort (n = 26). More over, knockdown of ESCCAL-1 expression increases esophageal cancer cell apoptosis and reduces the invasion in vitro. Our study uncovered the landscape of ESCC-associated lncRNAs. The systematic analysis of coding and lncRNAs co-expression network increases our understanding of lncRNAs in biological network. ESCCAL-1 is a novel putative onco-lncRNA in esophageal cancer development. The online version of this article (doi:10.1186/s12885-015-1179-z) contains supplementary material, which is available to authorized users.
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