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干扰素 1 型调控的 UBE2L6 作为结核病潜在标志物的研究

Increased UBE2L6 regulated by type 1 interferon as potential marker in TB.

机构信息

School of Medical Laboratory, Weifang Medical University, Weifang, China.

School of Basic Medicine, Weifang Medical University, Weifang, China.

出版信息

J Cell Mol Med. 2021 Dec;25(24):11232-11243. doi: 10.1111/jcmm.17046. Epub 2021 Nov 12.

Abstract

The aim of this study is to identify potential biomarker of tuberculosis (TB) and determine its function. Differentially expressed mRNAs(DEGs) were selected from a blood database GSE101805, and then, 30 key genes were screened using STING, Cytoscape and further functionally enriched. We then found that only 6 of 13 genes related to ubiquitination (the first in the functional enrichment) were increased significantly. ROC analysis showed that UBE2L6, among 6 genes, had the highest diagnostic value, and then, we found that it also had mild value in differential diagnosis. Moreover, our analysis showed that UBE2L6 may be upregulated by type I interferon, which was further confirmed by us. In addition, we also found that UBE2L6 inhibits the apoptosis of Mycobacterium tuberculosis(Mtb)infected macrophages. Subsequently, we discovered that miR-146a-5p, which may target UBE2L6, is reduced in peripheral blood mononuclear cells (PBMC) and plasma of TB, and it also had certain diagnostic efficiency(AUC=0.791). In brief, we demonstrated that UBE2L6 as well as miR-146a-5p is a potential biomarker for TB and UBE2L6,which may also plays important role in TB by, at least, modulating Mtb-infected macrophage apoptosis.

摘要

本研究旨在鉴定结核病(TB)的潜在生物标志物并确定其功能。从血液数据库 GSE101805 中选择差异表达的 mRNAs(DEGs),然后使用 STING、Cytoscape 筛选 30 个关键基因,并进一步进行功能富集。我们发现,在功能富集中排名第一的泛素化相关的 13 个基因中,仅有 6 个基因显著增加。ROC 分析表明,在这 6 个基因中,UBE2L6 的诊断价值最高,我们还发现它在鉴别诊断中也具有一定的价值。此外,我们的分析表明,UBE2L6 可能被 I 型干扰素上调,这一点也得到了我们的进一步证实。此外,我们还发现,UBE2L6 抑制分枝杆菌感染的巨噬细胞凋亡。随后,我们发现,miR-146a-5p 可能靶向 UBE2L6,其在外周血单核细胞(PBMC)和结核患者血浆中减少,且具有一定的诊断效率(AUC=0.791)。总之,我们证明 UBE2L6 及其靶基因 miR-146a-5p 是 TB 的潜在生物标志物,UBE2L6 可能通过调节分枝杆菌感染的巨噬细胞凋亡在结核病中发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1751/8650027/592d828b9793/JCMM-25-11232-g006.jpg

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