多药耐药结核病差异表达长非编码 RNA 的筛选和鉴定。
Screening and identification of differentially expressed long non-coding RNAs in multidrug-resistant tuberculosis.
机构信息
Department of Clinical Laboratory, Key Clinical Laboratory of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Clinical Laboratory, Henan Provincial Infectious Disease Hospital, Zhengzhou, China.
出版信息
PeerJ. 2022 Jan 17;10:e12776. doi: 10.7717/peerj.12776. eCollection 2022.
BACKGROUND
Efforts to eradicate tuberculosis are largely threatened by drug-resistant tuberculosis, particularly, multidrug-resistant tuberculosis (MDR-TB). Screening and identification potential biomarkers for MDR-TB is crucial to diagnose early and reduce the incidence of MDR-TB.
METHODS
To screen the differentially expressed long non-coding RNAs in MDR-TB, the lncRNA and mRNA expression profiles in serum derived from healthy controls (HCs), individuals with MDR-TB and drug-sensitive tuberculosis (DS-TB) were analyzed by microarray assay and 10 lncRNAs were randomly selected for further validation by reverse transcription-quantitative real-time PCR(RT-qPCR). The biological functions of differentially expressed mRNAs as well as relationships between genes and signaling pathways were investigated using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), respectively.
RESULTS
A total of 353 differentially expressed lncRNAs (312 upregulated) and 202 mRNAs (99 upregulated) were found in the MDR-TB group compared to HCs. And compared with the DS-TB group, 442 differentially expressed lncRNAs (115 upregulated) and 190 mRNAs (87 upregulated) were found in the MDR-TB group. The expression levels of lncRNA n335659 were found to differ significantly between each group by RT-qPCR. Compared with DS-TB group, the GO analysis showed that the differential mRNAs were mainly enriched in the processes associated with the detection of the chemical stimulus, the regulation of mRNA metabolic process and neutrophil activation in the MDR-TB group; the KEGG analysis indicated that the differential mRNAs between DS-TB and MDR-TB were mainly enriched in proteasome and Notch signaling pathway, which might reveal a fraction of the mechanism of MDR-TB. The discovery of the serum lncRNA n335659 might serve as a potential biomarker for MDR-TB and Notch signaling pathway provided a new clue for the investigation of the pathological mechanism of MDR-TB.
背景
消除结核病的努力在很大程度上受到耐药结核病的威胁，尤其是耐多药结核病（MDR-TB）。筛选和鉴定 MDR-TB 的潜在生物标志物对于早期诊断和降低 MDR-TB 的发病率至关重要。
方法
为了筛选 MDR-TB 中的差异表达长非编码 RNA，通过微阵列分析分析了来自健康对照（HC）、MDR-TB 患者和耐多药肺结核（DS-TB）患者的血清中的 lncRNA 和 mRNA 表达谱，并随机选择 10 个 lncRNA 通过逆转录定量实时 PCR（RT-qPCR）进一步验证。使用基因本体论（GO）和京都基因与基因组百科全书（KEGG）分别研究差异表达的 mRNAs 的生物学功能以及基因与信号通路之间的关系。
结果
与 HC 相比，MDR-TB 组中共有 353 个差异表达的 lncRNA（312 个上调）和 202 个 mRNA（99 个上调）。与 DS-TB 组相比，MDR-TB 组中有 442 个差异表达的 lncRNA（115 个上调）和 190 个 mRNA（87 个上调）。通过 RT-qPCR 发现 lncRNA n335659 的表达水平在各组之间存在显著差异。与 DS-TB 组相比，GO 分析表明差异 mRNAs 主要富集在与化学刺激检测、mRNA 代谢过程调节和中性粒细胞激活相关的过程中；KEGG 分析表明，DS-TB 和 MDR-TB 之间的差异 mRNAs 主要富集在蛋白酶体和 Notch 信号通路中，这可能揭示了 MDR-TB 的一部分机制。血清 lncRNA n335659 的发现可能作为 MDR-TB 的潜在生物标志物，Notch 信号通路为研究 MDR-TB 的病理机制提供了新线索。
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