Small RNA sequencing and bioinformatics analysis of RAW264.7-derived exosomes after Mycobacterium Bovis Bacillus Calmette-Guérin infection.

Small RNA sequencing and bioinformatics analysis of RAW264.7-derived exosomes after Mycobacterium Bovis Bacillus Calmette-Guérin infection.
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DOI:
10.1186/s12864-022-08590-w
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发表时间:
2022-05-07
期刊:
影响因子:
4.4
通讯作者:
--
中科院分区:
生物学2区
文献类型:
--
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结核分枝杆菌在结核病感染期间逃避免疫监测的机制仍然很复杂。以往的研究发现,分枝杆菌在宿主-病原体相互作用过程中可以操纵宿主细胞的miRNA来促进宿主细胞的存活,而这些作用大多发生在细胞miRNA水平。我们试图在外泌体miRNA水平上研究可能的相关机制。高通量测序结果显示,卡介苗(Bacillus calmette - gusamrin, BCG)感染可改变巨噬细胞外泌体的组成,巨噬细胞培养液中提取的外泌体中mirna的表达水平在感染和未感染组之间存在显著差异。与未感染组相比,感染组外泌体mirna上调20个,下调7个(p < 0.05),其中mmu-miR-27b-3p、mmu-miR-93-5p、mmu-miR-25-3p、mmu-miR-1198-5p、mmu-let-7c-5p、let-7a-5p显著上调。生物信息学分析表明,这些差异表达的外泌体mirna参与了多种生物学过程和途径。上调组前6位mirna的靶基因与细胞凋亡调控呈正相关。牛分枝杆菌感染巨噬细胞外泌体miRNA表达谱发生改变,差异表达的miRNA参与多种生物学过程和信号通路。上调前6位的mirna及其靶基因与细胞凋亡的调控主要相关。
The mechanisms through which Mycobacterium tuberculosis evades immune surveillance during tuberculosis (TB) infection remain complex. Previous studies have found that Mycobacteria can manipulate the miRNAs of host cells to promote their survival during host-pathogen interactions, and most of these effects occur at the cellular miRNA level. We attempted to investigate the possible related mechanisms at the exosomal miRNA level. High-throughput sequencing revealed that Bacillus Calmette-Guérin (BCG) infection could alter the composition of the macrophage exosome content, and the expression levels of miRNAs in exosomes derived from the cell culture media of macrophages showed significant differences between the BCG-infected and non-infected groups. Compared with the non-infected group, 20 exosomal miRNAs were up-regulated and 7 exosomal miRNAs were down-regulated in the infection group (p < 0.05), of which mmu-miR-27b-3p, mmu-miR-93-5p, mmu-miR-25-3p, mmu-miR-1198-5p, mmu-let-7c-5p and let-7a-5p were significantly up-regulated. A bioinformatic analysis indicated that these differentially expressed exosomal miRNAs were involved in multiple biological processes and pathways. The target genes of top six miRNAs in up-regulated groups were positively correlated with the regulation of apoptosis. The expression profile of miRNA in exosomes derived from macrophage were altered after Mycobacterium Bovis Bacillus Calmette-Guérin infection, and the differentially expressed miRNAs were involved in multiple biological processes and signalling pathways. The top six up-regulated miRNAs and their targeted genes were predominantly correlated with the regulation of apoptosis.
来自耐药乳腺癌细胞的外泌体通过 MicroRNA 的水平转移传递化疗耐药性
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