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通过微阵列揭示的膀胱癌长链非编码RNA表达特征

Long noncoding RNA expression signatures of bladder cancer revealed by microarray.

作者信息

Zhu Yi-Ping, Bian Xiao-Jie, Ye Ding-Wei, Yao Xu-Dong, Zhang Shi-Lin, Dai Bo, Zhang Hai-Liang, Shen Yi-Jun

机构信息

Department of Urology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, P.R. China ; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China.

出版信息

Oncol Lett. 2014 Apr;7(4):1197-1202. doi: 10.3892/ol.2014.1843. Epub 2014 Jan 31.

Abstract

Dysregulation of long noncoding RNAs (lncRNAs) has been regarded as a primary feature of several human cancers. However, the genome-wide expression and functional significance of lncRNAs in bladder cancer remains unclear. The aim of this study was to identify aberrantly expressed lncRNAs that may play an important role in contributing to bladder cancer pathogenesis. In this study, we described lncRNAs profiles in four pairs of human bladder cancer and matched normal bladder tissues by microarray. We finally determined 3,324 differentially expressed human lncRNAs and 2,120 differentially expressed mRNAs (≥2-fold change). A total of 110 lncRNAs were significantly differentially expressed between the tumor and the control groups (≥8-fold change). Four lncRNAs (TNXA, CTA-134P22.2, CTC-276P9.1 and KRT19P3) were selected for further confirmation of microarray results using quantitative PCR (qPCR), and a strong correlation was identified between the qPCR results and microarray data. We also observed that numerous lncRNA expression levels were significantly correlated with the expression of tens of protein coding genes by construction of the lncRNA-mRNA co-expression network. Kyoto Encyclopedia of Genes and Genomes annotation showed a significant association with p53, bladder cancer, cell cycle and propanoate metabolism pathway gene expression in the bladder cancer group compared with the normal tissue group, indicating that deregulated lncRNAs may act by regulating protein-coding genes in these pathways. We demonstrated the expression profiles of human lncRNAs in bladder cancer by microarray. We identified a collection of aberrantly expressed lncRNAs in bladder cancer compared with matched normal tissue. It is likely that these deregulated lncRNAs play a key or partial role in the development and/or progression of bladder cancer.

摘要

长链非编码RNA(lncRNAs)的失调被认为是几种人类癌症的主要特征。然而,lncRNAs在膀胱癌中的全基因组表达及功能意义仍不清楚。本研究的目的是鉴定可能在膀胱癌发病机制中起重要作用的异常表达的lncRNAs。在本研究中,我们通过微阵列描述了四对人膀胱癌组织及配对的正常膀胱组织中的lncRNAs图谱。我们最终确定了3324个差异表达的人类lncRNAs和2120个差异表达的mRNA(≥2倍变化)。肿瘤组和对照组之间共有110个lncRNAs显著差异表达(≥8倍变化)。选择了四个lncRNAs(TNXA、CTA-134P22.2、CTC-276P9.1和KRT19P3),使用定量PCR(qPCR)进一步确认微阵列结果,并且qPCR结果与微阵列数据之间存在很强的相关性。通过构建lncRNA-mRNA共表达网络,我们还观察到许多lncRNA表达水平与数十个蛋白质编码基因的表达显著相关。与正常组织组相比,京都基因与基因组百科全书注释显示膀胱癌组中lncRNAs失调可能通过调节这些途径中的蛋白质编码基因发挥作用,这与p53、膀胱癌、细胞周期和丙酸代谢途径基因表达显著相关。我们通过微阵列展示了人lncRNAs在膀胱癌中的表达谱。与配对的正常组织相比,我们在膀胱癌中鉴定出了一组异常表达的lncRNAs。这些失调的lncRNAs很可能在膀胱癌的发生和/或进展中起关键或部分作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f71/3961449/ee8b58425f1b/OL-07-04-1197-g00.jpg

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