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乳头状甲状腺癌中长链非编码RNA表达谱的全基因组分析。

Genome-wide analysis of long noncoding RNA expression profile in papillary thyroid carcinoma.

作者信息

Lan Xiabin, Zhang Hao, Wang Zhihong, Dong Wenwu, Sun Wei, Shao Liang, Zhang Ting, Zhang Dalin

机构信息

Department of Thyroid Surgery, The First Hospital of China Medical University, No. 155, Nanjing Bei Street, Heping District, Shenyang 110001, Liaoning Province, People's Republic of China.

Department of Thyroid Surgery, The First Hospital of China Medical University, No. 155, Nanjing Bei Street, Heping District, Shenyang 110001, Liaoning Province, People's Republic of China.

出版信息

Gene. 2015 Sep 10;569(1):109-17. doi: 10.1016/j.gene.2015.05.046. Epub 2015 May 21.

Abstract

Long noncoding RNAs (lncRNAs) have been proved to play important roles in cancer biology. To understand their expression profile and potential functions in papillary thyroid carcinoma (PTC), we investigated the lncRNA and mRNA expression in PTC and paired adjacent noncancerous thyroid tissue using microarray. Quantitative real time polymerase chain reaction (qRT-PCR) was used to validate 10 differentially expressed lncRNAs. Gene ontology (GO) analysis and pathway analysis were also used to investigate the gene function. Potential target genes of lncRNAs were predicted according to two independent algorithms. The microarray revealed thousands of significantly differentially expressed lncRNAs and mRNAs in PTC relative to noncancerous thyroid tissue. The results of qRT-PCR were consistent with those of the microarray, in that all 10 lncRNAs were differentially expressed with the same trend (up- or down-regulated) (P<0.05). Significantly enriched GO terms and pathways among differentially expressed mRNAs were identified. Many of these pathways were linked to cancer, such as "p53 signaling pathway" (associated with 25 genes), "pathways in cancer" (associated with 75 genes), "MAPK signaling pathway" (associated with 50 genes) and "PPAR signaling pathway" (associated with 16 genes). 1805 dysregulated lncRNAs were found to have cis or trans target genes. 463 of the cis target genes were found to be differentially expressed and might be regulated by lncRNAs in the tumorigenesis of PTC. Our study provides a genome-wide screening and analysis of lncRNA expression profile in PTC for the first time and lays the foundation for further investigation of lncRNAs related to PTC.

摘要

长链非编码RNA(lncRNAs)已被证明在癌症生物学中发挥重要作用。为了解它们在甲状腺乳头状癌(PTC)中的表达谱及潜在功能,我们使用微阵列技术研究了PTC及配对的相邻非癌甲状腺组织中的lncRNA和mRNA表达。采用定量实时聚合酶链反应(qRT-PCR)验证10个差异表达的lncRNAs。还利用基因本体(GO)分析和通路分析来研究基因功能。根据两种独立算法预测lncRNAs的潜在靶基因。微阵列显示,与非癌甲状腺组织相比,PTC中有数千个lncRNAs和mRNAs存在显著差异表达。qRT-PCR结果与微阵列结果一致,即所有10个lncRNAs均呈相同趋势(上调或下调)差异表达(P<0.05)。确定了差异表达mRNA中显著富集的GO术语和通路。其中许多通路与癌症相关,如“p53信号通路”(与25个基因相关)、“癌症通路”(与75个基因相关)、“MAPK信号通路”(与50个基因相关)和“PPAR信号通路”(与16个基因相关)。发现1805个失调的lncRNAs具有顺式或反式靶基因。其中463个顺式靶基因被发现差异表达,可能在PTC的肿瘤发生过程中受lncRNAs调控。我们的研究首次对PTC中的lncRNA表达谱进行了全基因组筛选和分析,为进一步研究与PTC相关的lncRNAs奠定了基础。

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