State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
Int J Biol Sci. 2012;8(7):1013-22. doi: 10.7150/ijbs.3836. Epub 2012 Aug 3.
MicroRNA (miRNA) is small non-coding RNA with approximate 22 nt in length. Recent studies indicate that miRNAs play significant roles in pathogen-host interactions. Brucella organisms are Gram-negative facultative intracellular bacteria that cause Brucellosis. Brucella strains infect macrophages and establish chronic infection by altering host life activities including apoptosis and autophagy. Here, we report a comprehensive analysis of miRNA expression profiles in mock- and Brucella-infected RAW264.7 cells using high-throughput sequencing approach. In total, 344 unique miRNAs were co-expressed in the two libraries, in which 57 miRNAs were differentially expressed. Eight differentially expressed miRNAs with high abundance were subjected to further analysis. The GO enrichment analysis suggests that the putative target genes of these differentially expressed miRNAs are involved in apoptosis, autophagy and immune response. In particular, a total of 25 target genes are involved in regulating apoptosis and autophagy, indicating that these miRNAs may play important regulatory roles in the Brucella-host interactions. Furthermore, the interactions of miR-1981 and its target genes, Bcl-2 and Bid, were validated by luciferase assay. The results show that miR-1981 mimic up-regulated the luciferase activity of psiCHECK-2 Bcl-2 3' UTR, but the luciferase activity of psiCHECK-2 Bid 3' UTR was not changed significantly. Taken together, these data provide valuable framework on Brucella induced miRNA expression in RAW264.7 cells, and suggest that Brucella may establish chronic infection by regulating miRNA expression profile.
微小 RNA(miRNA)是一种大约 22 个核苷酸长度的小型非编码 RNA。最近的研究表明,miRNA 在病原体-宿主相互作用中发挥重要作用。布鲁氏菌是革兰氏阴性兼性细胞内细菌,可引起布鲁氏菌病。布鲁氏菌菌株通过改变宿主的生命活动,包括细胞凋亡和自噬,感染巨噬细胞并建立慢性感染。在这里,我们使用高通量测序方法报告了模拟和布鲁氏菌感染 RAW264.7 细胞中 miRNA 表达谱的全面分析。在这两个文库中,共有 344 个独特的 miRNA 共同表达,其中 57 个 miRNA 表达差异。对 8 个高丰度的差异表达 miRNA 进行了进一步分析。GO 富集分析表明,这些差异表达 miRNA 的假定靶基因参与细胞凋亡、自噬和免疫反应。特别是,共有 25 个靶基因参与调节细胞凋亡和自噬,表明这些 miRNA 可能在布鲁氏菌-宿主相互作用中发挥重要的调节作用。此外,通过荧光素酶测定验证了 miR-1981 与其靶基因 Bcl-2 和 Bid 的相互作用。结果表明,miR-1981 模拟物上调了 psiCHECK-2 Bcl-2 3'UTR 的荧光素酶活性,但 psiCHECK-2 Bid 3'UTR 的荧光素酶活性没有明显变化。总之,这些数据为 RAW264.7 细胞中布鲁氏菌诱导的 miRNA 表达提供了有价值的框架,并表明布鲁氏菌可能通过调节 miRNA 表达谱来建立慢性感染。