The State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China.
College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
Int J Mol Sci. 2021 Dec 29;23(1):382. doi: 10.3390/ijms23010382.
Although (MTB) has existed for thousands of years, its immune escape mechanism remains obscure. Increasing evidence signifies that microRNAs (miRNAs) play pivotal roles in the progression of tuberculosis (TB). RNA sequencing was used to sequence miRNAs in human acute monocytic leukemia cells (THP-1) infected by the virulent MTB-1458 strain and the avirulent vaccine strain Bacillus Calmette-Guérin (BCG). Sets of differentially expressed miRNAs (DE-miRNAs) between MTB-1458/BCG-infected groups and uninfected groups were identified, among which 18 were differentially expressed only in the MTB-1458-infected THP-1 group. Then, 13 transcription factors (TFs) and 81 target genes of these 18 DE-miRNAs were matched. Gene Ontology classification as well as Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the candidate targets were predominantly involved in apoptotic-associated and interferon-γ-mediated signaling pathways. A TF-miRNA-mRNA interaction network was constructed to analyze the relationships among these 18 DE-miRNAs and their targets and TFs, as well as display the hub miRNAs, TFs, and target genes. Considering the degrees from network analysis and the reported functions, this study focused on the BHLHE40-- regulation axis and confirmed that was a target of . This cross-talk among DE-miRNAs, mRNAs, and TFs might be an important feature in TB, and the findings merited further study and provided new insights into immune defense and evasion underlying host-pathogen interactions.
尽管（MTB）已经存在了数千年，但它的免疫逃逸机制仍然不清楚。越来越多的证据表明，microRNAs（miRNAs）在结核病（TB）的进展中起着关键作用。使用 RNA 测序对感染强毒 MTB-1458 株和弱毒卡介苗（BCG）株的人急性单核细胞白血病细胞（THP-1）中的 miRNAs 进行测序。在 MTB-1458/BCG 感染组和未感染组之间鉴定了一组差异表达的 miRNAs（DE-miRNAs），其中 18 个仅在 MTB-1458 感染的 THP-1 组中差异表达。然后，匹配了这 18 个 DE-miRNA 的 13 个转录因子（TF）和 81 个靶基因。基因本体分类和京都基因与基因组百科全书通路富集分析表明，候选靶标主要参与凋亡相关和干扰素-γ介导的信号通路。构建了一个 TF-miRNA-mRNA 相互作用网络，以分析这 18 个 DE-miRNA 及其靶基因和 TF 之间的关系，并显示出 hub miRNAs、TFs 和靶基因。考虑到网络分析和已报道功能的程度，本研究重点关注了 BHLHE40--调节轴，并证实 是 的靶基因。DE-miRNAs、mRNAs 和 TFs 之间的这种串扰可能是 TB 的一个重要特征，研究结果值得进一步研究，并为宿主-病原体相互作用的免疫防御和逃逸提供了新的见解。
