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通过RNA测序对食管鳞状细胞癌中lncRNA的转录组分析及共表达网络研究

Transcriptome profiling of lncRNA and co-expression networks in esophageal squamous cell carcinoma by RNA sequencing.

作者信息

Li Yuan, Shi Xuejiao, Yang Wenhui, Lu Zhiliang, Wang Pan, Chen Zhaoli, He Jie

机构信息

Department of Thoracic Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuannanli, Beijing, 100021, China.

Department of Oncology, the First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.

出版信息

Tumour Biol. 2016 Oct;37(10):13091-13100. doi: 10.1007/s13277-016-5227-3. Epub 2016 Jul 23.

Abstract

Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of cancer. To identify novel targets for further study in esophageal squamous cell carcinoma (ESCC), we performed a genome-wide analysis of lncRNA expression in 12 ESCC tumor and normal tissues. Publicly available RNA-seq data were downloaded from the NCBI, GEO, and Co-LncRNA databases, and lncRNA and messenger RNA (mRNA) expression profiles were analyzed. In total, 127 lncRNAs were found to be differentially expressed, with a greater than fourfold change in ESCC tumor tissues compared with normal tissues. Among these lncRNAs, 98 were upregulated and 29 downregulated. Moreover, 1469 network nodes and 1720 connection edges between 119 lncRNAs and 1350 coding genes were integrated into the lncRNA and mRNA co-expression network. Bioinformatic analysis using GO terms revealed that these dysregulated lncRNAs are associated with developmental processes, proteinaceous extracellular matrix, and protein binding activity, with ECM-receptor interaction and the PI3K-Akt signaling pathway enrichment. Lastly, qRT-PCR results verified two significantly upregulated lncRNAs and three significantly downregulated lncRNAs in 50 pairs of ESCC tissues and adjacent normal tissues. These results reveal the landscape of ESCC-associated lncRNAs and co-expression networks, providing important insight regarding the lncRNAs involved in ESCC.

摘要

长链非编码RNA(lncRNAs)正逐渐成为癌症的关键调节因子。为了确定在食管鳞状细胞癌(ESCC)中进一步研究的新靶点,我们对12例ESCC肿瘤组织和正常组织中的lncRNA表达进行了全基因组分析。从NCBI、GEO和Co-LncRNA数据库下载公开可用的RNA-seq数据,并分析lncRNA和信使RNA(mRNA)表达谱。总共发现127种lncRNAs存在差异表达,与正常组织相比,ESCC肿瘤组织中的变化大于四倍。在这些lncRNAs中,98种上调,29种下调。此外,119种lncRNAs与1350个编码基因之间的1469个网络节点和1720条连接边被整合到lncRNA和mRNA共表达网络中。使用GO术语进行的生物信息学分析表明,这些失调的lncRNAs与发育过程、蛋白质细胞外基质和蛋白质结合活性相关,富集于ECM-受体相互作用和PI3K-Akt信号通路。最后,qRT-PCR结果验证了50对ESCC组织及相邻正常组织中两种显著上调的lncRNAs和三种显著下调的lncRNAs。这些结果揭示了ESCC相关lncRNAs和共表达网络的概况,为参与ESCC的lncRNAs提供了重要见解。

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