Microarray expression profile analysis of long non-coding RNAs in pancreatic ductal adenocarcinoma

Microarray expression profile analysis of long non-coding RNAs in pancreatic ductal adenocarcinoma
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胰腺导管腺癌中长非编码RNA的微阵列表达谱分析

DOI:
10.3892/ijo.2015.3292
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发表时间:
2016-02-01
影响因子:
5.2
通讯作者:
Zhu, Shi-Kai
Zhu, Shi-Kai
中科院分区:
医学2区
文献类型:
--
作者:
Zhou, Yu;Gong, Bo;Zhu, Shi-Kai

文献摘要

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长链非编码RNA (Long non-coding RNA, lncRNA)是一种不编码蛋白质的人类转录组,在多种实体恶性肿瘤的发生发展中发挥着重要作用。然而,lncrna在胰腺导管腺癌(PDAC)发展中的作用尚不清楚。在这项研究中,我们通过一个包含30,586个lncRNA探针和26,109个mRNA探针的微阵列,研究了三个PDAC肿瘤样本(T)相对于匹配的邻近非肿瘤组织(N)的lncRNA表达模式。lncRNA芯片显示,与匹配的邻近非肿瘤样本相比,PDAC样本中有27279个lncRNA,其中2331个显著上调(P2.0), 1641个下调(P2.0)。此外,检测到19,995个mrna,其中1,676个显著上调(P2.0), 1,981个下调(P2.0)。通路分析显示,41条通路对应上调转录本,25条通路对应下调转录本(p值临界值为0.05)。基因本体(Gene ontology, GO)分析显示,上调和下调转录本所针对的GO富集程度最高的是组织稳态。定量反转录聚合酶链反应(qRT-PCR)和芯片分析的验证结果一致。此外,通过qRT-PCR,与匹配的邻近非肿瘤样本相比,12个PDAC组织样本中长基因间非编码RNA HOTAIRM1的表达水平上调。结果显示,lncRNA和mRNA的表达谱在PDAC组织与其邻近的非肿瘤组织之间存在显著差异,HOTAIRM1表达与PDAC之间的关联尤其值得关注。这些发现可能为PDAC的诊断和治疗提供新的潜在分子标记。
Long non-coding RNA (lncRNA) is a variety of the human transcriptome that does not code for proteins and plays an important role in the development and progression of multiple solid malignant tumors. However, the roles of lncRNAs in the development of pancreatic ductal adenocarcinoma (PDAC) remain unknown. In this study, we investigated the expression patterns of lncRNAs in three PDAC tumor samples (T) relative to those of matched adjacent non-tumor tissues (N) via a microarray with 30,586 lncRNA probes and 26,109 mRNA probes. The lncRNA microarray revealed 27,279 lncRNAs in PDAC samples, of which 2,331 were significantly upregulated (P2.0) and 1,641 were downregulated (P2.0) compared with matched adjacent non-tumor samples. In addition, 19,995 mRNAs were detected, of which 1,676 were significantly upregulated (P2.0) and 1,981 were downregulated (P2.0). Pathway analysis indicated that 41 pathways corresponded to upregulated transcripts and 25 pathways corresponded to downregulated transcripts (P-value cut-off is 0.05). Gene ontology (GO) analysis showed that the highest enriched GOs targeted by upregulated and downregulated transcripts were tissue homeostasis. The validation results from quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis and microarray analysis were consistent. Furthermore, the expression level of long intergenic non-coding RNA HOTAIRM1 was upregulated in 12 PDAC tissues samples compared with matched adjacent non-tumor samples by qRT-PCR. The results showed that the lncRNA and mRNA expression profiles differed significantly between the PDAC tissues and their adjacent non-tumor tissues, and the revelation of an association between HOTAIRM1 expression and PDAC is especially noteworthy. These findings may provide new potential molecular markers for diagnosis and treatment of PDAC.