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外周血单个核细胞中长链非编码 RNA 对儿童结核病反应的异常表达。

Aberrant expression of long non-coding RNAs in peripheral blood mononuclear cells response to tuberculosis in children.

机构信息

West China Second Hospital, Sichuan University/ Key Laboratory of Birth Defects and Related Diseases of Women and Children,Sichuan University, Ministry of Education, Chengdu, PR China.

The Third People's Hospital of Chengdu/The Affiliated Hospital of Southwest Jiaotong University, Chengdu, PR China.

出版信息

Medicine (Baltimore). 2022 Oct 21;101(42):e31065. doi: 10.1097/MD.0000000000031065.

Abstract

We aimed to identify long non-coding RNAs (lncRNAs) aberrantly expressed in peripheral blood mononuclear cells (PBMCs) triggered by active tuberculosis (ATB), latent tuberculosis infection (LTBI), and healthy controls (HC). We examined lncRNAs expression in PBMCs isolated from children with ATB and LTBI, and from HC using RNA sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to explore the biological processes and signaling pathways of aberrantly expressed mRNAs. A total of 348 and 205 lncRNAs were differentially expressed in the ATB and LTBI groups, respectively, compared to the HC group. Compared to the LTBI group, 125 lncRNAs were differentially expressed in the ATB group. Compared to the HC group, 2317 mRNAs were differentially expressed in the ATB group, and 1093 mRNAs were differentially expressed in the LTBI group. Compared to the LTBI group, 2328 mRNAs were differentially expressed in the ATB group. The upregulated mRNAs were mainly enriched in neutrophil activation, neutrophil-mediated biological processes, and positive regulation of immune response in tuberculosis (TB), whereas the downregulated mRNAs were enriched in signaling pathways and structural processes, such as the Wnt signaling pathway and rDNA heterochromatin assembly. This is the first study on the differential expression of lncRNAs in PBMCs of children with TB. We identified significant differences in the expression profiles of lncRNAs and mRNAs in the PBMCs of children with ATB, LTBI, and HC, which has important implications for exploring lncRNAs as novel biomarkers for the diagnosis of TB. In addition, further experimental identification and validation of lncRNA roles could help elucidate the underlying mechanisms of Mycobacterium tuberculosis infection in children.

摘要

我们旨在鉴定由活动性肺结核(ATB)、潜伏性结核感染(LTBI)和健康对照(HC)引发的外周血单个核细胞(PBMC)中异常表达的长非编码 RNA(lncRNAs)。我们使用 RNA 测序检测了来自 ATB 和 LTBI 患儿以及 HC 的 PBMC 中 lncRNAs 的表达。通过基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路分析,探讨了异常表达 mRNAs 的生物学过程和信号通路。与 HC 组相比,ATB 组和 LTBI 组分别有 348 个和 205 个 lncRNAs 表达差异。与 LTBI 组相比,ATB 组有 125 个 lncRNAs 表达差异。与 HC 组相比,ATB 组有 2317 个 mRNAs 表达差异,LTBI 组有 1093 个 mRNAs 表达差异。与 LTBI 组相比,ATB 组有 2328 个 mRNAs 表达差异。上调的 mRNAs 主要富集于中性粒细胞激活、中性粒细胞介导的生物学过程以及结核病(TB)中的免疫反应的正调控,而下调的 mRNAs 则富集于信号通路和结构过程,如 Wnt 信号通路和 rDNA 异染色质组装。这是第一项关于 TB 患儿 PBMC 中 lncRNAs 差异表达的研究。我们发现 ATB、LTBI 和 HC 患儿 PBMC 中 lncRNAs 和 mRNAs 的表达谱存在显著差异,这对探索 lncRNAs 作为 TB 诊断的新型生物标志物具有重要意义。此外,进一步对 lncRNA 作用的实验鉴定和验证有助于阐明儿童中结核分枝杆菌感染的潜在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4763/9592404/b6b54470b188/medi-101-e31065-g001.jpg

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