He Jun-Jun, Ma Jun, Wang Jin-Lei, Xu Min-Jun, Zhu Xing-Quan
State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province 730046, PR China.
State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province 730046, PR China; College of Veterinary Medicine, Hunan Agricultural University, Changsha, Hunan Province 410128, PR China.
Infect Genet Evol. 2016 Jan;37:137-42. doi: 10.1016/j.meegid.2015.11.005. Epub 2015 Nov 10.
Toxoplasma gondii is a worldwide prevalent pathogen that infects most of the warm-blood vertebrates. To investigate the regulation network of splenic miRNAs altered by acute infection with T. gondii, we herein investigated the changes of miRNA profile in mouse spleen via next generation sequencing and bioinformatics analysis. A total of 379 miRNAs was identified, 131 miRNAs of them were differentially expressed (including 97 upregulated and 34 downregulated miRNAs). 48 differentially expressed miRNAs had validated targets in the miRWalk2.0 database. Gene Ontology (GO) enrichment analysis revealed that the validated targets of differently expressed miRNAs were significantly enriched in gene transcription regulation. It suggested that T. gondii can modulate host gene expression through targeting to trans-regulation factors. The genes involved in apoptosis or anti-apoptosis were both targeted by differentially expressed miRNAs. The change of power balance between the miRNAs targeting host apoptosis genes and those regulating host anti-apoptosis genes contributes to the fate of host apoptosis process. Twelve pathways were significantly enriched in KEGG analysis with most of them being cancer related, including pathways in cancer, pancreatic cancer, colorectal cancer, axon guidance, MAPK signaling pathway, focal adhesion, chronic myeloid leukemia, renal cell carcinoma, prostate cancer, glioma, regulation of actin cytoskeleton, and Wnt signaling pathway. Our study showed a changed miRNA regulation network in mouse spleen infected by T. gondii. These findings will be helpful for better understanding of miRNA regulation network in host-T. gondii interaction, revealing the relationship among T. gondii infection, gene regulation, apoptosis and cancer process alterations in infected spleen.
弓形虫是一种在全球广泛流行的病原体,可感染大多数温血脊椎动物。为了研究急性感染弓形虫后脾脏微小RNA(miRNA)的调控网络,我们通过下一代测序和生物信息学分析,研究了小鼠脾脏中miRNA谱的变化。共鉴定出379个miRNA,其中131个miRNA存在差异表达(包括97个上调和34个下调的miRNA)。48个差异表达的miRNA在miRWalk2.0数据库中有经过验证的靶标。基因本体论(GO)富集分析显示,差异表达miRNA的经过验证的靶标在基因转录调控方面显著富集。这表明弓形虫可通过靶向反式调节因子来调节宿主基因表达。参与凋亡或抗凋亡的基因均被差异表达的miRNA靶向。靶向宿主凋亡基因的miRNA与调节宿主抗凋亡基因的miRNA之间的力量平衡变化,影响宿主凋亡进程的命运。京都基因与基因组百科全书(KEGG)分析中有12条通路显著富集,其中大部分与癌症相关,包括癌症通路、胰腺癌通路、结直肠癌通路、轴突导向通路、丝裂原活化蛋白激酶(MAPK)信号通路、粘着斑通路、慢性髓性白血病通路、肾细胞癌通路、前列腺癌通路、神经胶质瘤通路、肌动蛋白细胞骨架调节通路和Wnt信号通路。我们的研究表明,感染弓形虫的小鼠脾脏中miRNA调控网络发生了变化。这些发现将有助于更好地理解宿主-弓形虫相互作用中的miRNA调控网络,揭示弓形虫感染、基因调控、凋亡与感染脾脏中癌症进程改变之间的关系。