Deregulated microRNAs in CD4+ T cells from individuals with latent tuberculosis versus active tuberculosis.

Deregulated microRNAs in CD4+ T cells from individuals with latent tuberculosis versus active tuberculosis.
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潜伏性结核病患者与活动性结核病患者的 CD4 T 细胞中的 microRNA 失调

DOI:
10.1111/jcmm.12205
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发表时间:
2014-03
影响因子:
5.3
通讯作者:
Li R
Li R
中科院分区:
医学2区
文献类型:
--
作者:
Fu Y;Yi Z;Li J;Li R

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潜伏性结核病(TB)感染的机制仍然难以捉摸。microRNA(microRNA,miRNA)在病原体与宿主相互作用中的作用日益受到重视。为了鉴定参与对TB的免疫应答的miRNA,通过微阵列测定研究了来自潜伏性TB患者、活动性TB患者和健康对照的CD 4 + T细胞中的miRNA表达谱,并通过RT-qPCR验证。采用基因本体论(GO)和京都基因与基因组百科全书(KEGG)途径分析差异表达的miRNA的重要功能和参与信号通路。为了鉴定miR-29的潜在靶基因,通过RT-qPCR测量干扰素-γ(IFN-γ)mRNA表达。我们的研究结果显示,27个miRNAs在三组中表达失调。RT-qPCR结果与微阵列数据基本一致。我们观察到CD 4 + T细胞中miR-29水平与IFN-γ mRNA表达之间呈负相关。GO和KEGG通路分析显示,去调控的miRNAs可能的靶基因在丝裂原活化蛋白激酶信号通路、粘着斑和细胞外基质受体相互作用中显著富集,这些基因可能参与了潜伏性结核向活动性结核的转变。总之,我们的研究首次揭示了潜伏性和活动性TB中CD 4 + T细胞中的一些miRNA发生了改变。功能和途径分析强调了miRNA失调的mRNA在TB中的可能参与。该研究有助于加深对CD 4 + T细胞中miRNAs与结核病关系的认识,为进一步阐明结核病潜伏感染及其再激活的机制奠定了重要基础。
The mechanisms of latent tuberculosis (TB) infection remain elusive. Roles of microRNA (miRNA) have been highlighted in pathogen–host interactions recently. To identify miRNAs involved in the immune response to TB, expression profiles of miRNAs in CD4+ T cells from patients with latent TB, active TB and healthy controls were investigated by microarray assay and validated by RT-qPCR. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to analyse the significant functions and involvement in signalling pathways of the differentially expressed miRNAs. To identify potential target genes for miR-29, interferon-γ (IFN-γ) mRNA expression was measured by RT-qPCR. Our results showed that 27 miRNAs were deregulated among the three groups. RT-qPCR results were generally consistent with the microarray data. We observed an inverse correlation between miR-29 level and IFN-γ mRNA expression in CD4+ T cells. GO and KEGG pathway analysis showed that the possible target genes of deregulated miRNAs were significantly enriched in mitogen-activated protein kinase signalling pathway, focal adhesion and extracellular matrix receptor interaction, which might be involved in the transition from latent to active TB. In all, for the first time, our study revealed that some miRNAs in CD4+ T cells were altered in latent and active TB. Function and pathway analysis highlighted the possible involvement of miRNA-deregulated mRNAs in TB. The study might help to improve understanding of the relationship between miRNAs in CD4+ T cells and TB, and laid an important foundation for further identification of the underlying mechanisms of latent TB infection and its reactivation.
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