Screening and identification of lncRNAs as potential biomarkers for pulmonary tuberculosis.

Screening and identification of lncRNAs as potential biomarkers for pulmonary tuberculosis.
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筛选和鉴定作为肺结核潜在生物标志物的lncRNA

DOI:
10.1038/s41598-017-17146-y
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发表时间:
2017-12-01
期刊:
影响因子:
4.6
通讯作者:
Li JC
Li JC
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chen ZL;Wei LL;Shi LY;Li M;Jiang TT;Chen J;Liu CM;Yang S;Tu HH;Hu YT;Gan L;Mao LG;Wang C;Li JC

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肺结核是世界范围内发病率和死亡率最高的疾病之一。缺乏有效的结核病诊断方法。在本研究中,我们利用微阵列技术研究了血浆中的长非编码RNA(LncRNAs)及其对结核病的潜在诊断价值。我们共发现163个上调的LncRNA和348个下调的LncRNAs。基因本体论(GO)、京都基因与基因组百科全书(KEGG)和编码-非编码共表达(CNC)分析表明,差异表达的lncRNAs的功能主要集中在调节α-βT细胞激活和T细胞受体信号通路上。4个差异表达的LncRNA分别为:NR_038221(Fold Change = 3.79,P < 0.01)、NR_003142(Fold Change = 1.69,P < 0.05)、ENST00000570366(Fold Change = 3.04,P < 0.05)和ENST00000422183(Fold Change = 2.11,P < 0.001)。其中,NR_038221、NR_003142和ENST00000570366基因表达上调,ENST00000422183基因表达下调。由4个LncRNA组成的诊断模型的曲线下面积(AUC值)为0.845(敏感性 = 为79.2%,特异性 = 为75%)。我们进一步预测了85个mRNAs和404个miRNAs可能与这些lncRNAs相互作用。我们的研究揭示了lncRNAs作为结核病早期诊断生物标志物的潜在价值,以及这些异常表达的lncRNAs在结核病发病机制中的潜在机制。
Pulmonary tuberculosis (TB) is among the diseases with the highest morbidity and mortality worldwide. Effective diagnostic methods for TB are lacking. In this study, we investigated long non-coding RNAs (lncRNAs) in plasma using microarray and the potential diagnostic value of lncRNAs for TB. We found a total of 163 up-regulated lncRNAs and 348 down-regulated lncRNAs. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and coding-noncoding co-expression (CNC) analyses showed that functions of differentially expressed lncRNAs were mainly enriched in the regulation of alpha-beta T cell activation and the T cell receptor signalling pathway. Four differentially expressed lncRNAs, NR_038221 (fold change = 3.79, P < 0.01), NR_003142 (fold change = 1.69, P < 0.05), ENST00000570366 (fold change = 3.04, P < 0.05), and ENST00000422183 (fold change = 2.11, P < 0.001), were verified using RT-qPCR. Among those, NR_038221, NR_003142, and ENST00000570366 were found to be up-regulated, while ENST00000422183 was down-regulated. The value of the area under the curve (AUC) for the diagnostic model consisting of the four lncRNAs was 0.845 (sensitivity = 79.2%, specificity = 75%). We further predicted 85 mRNAs and 404 miRNAs that potentially interact with these lncRNAs. Our study revealed the potential value of lncRNAs as biomarkers for early diagnosis of TB and the underlying mechanisms of these abnormally expressed lncRNAs in the pathogenesis of TB.
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