华支睾吸虫细胞外囊泡中miRNAs调控宿主靶基因的预测及生物信息学分析

Prediction and bioinformatic analysis of host target genes regulated by miRNAs in the extracellular membrane vesicles of Clonorchis sinensis

为了评估华支睾吸虫(Clonorchis sinensis)细胞外膜囊泡中虫源miRNAs跨物种调控宿主基因的风险,试验利用miRBase数据库对华支睾吸虫细胞外膜囊泡和感染阳性宿主细胞共有的虫源miRNAs成熟体序列进行筛选,通过miRanda软件对细胞外膜囊泡中表达量排在前10位的miRNAs进行靶基因预测,选取每个miRNAs评分排在前10位的靶基因作为候选靶基因,通过NCBI、Bing检索工具检索miRNAs候选靶基因的功能,利用GO功能注释及KEGG富集分析对靶基因进行生物信息学分析。结果表明:华支睾吸虫细胞外膜囊泡中的10种miRNAs共对应8128个与宿主相关的靶基因。有12个候选靶基因没有相关的功能报道,12个候选靶基因与肝功能有关,其余候选靶基因在癌症、信号转导、结构骨架、增殖和分化、迁移功能中发挥重要作用。候选靶基因Taf10和Onecut2与肝脏和肝胆管发育相关,候选靶基因Gng1和Hhip分别可参与致纤维化相关的丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)和Hedgehog信号通路。说明虫源miRNAs有靶向宿主细胞并参与致宿主肝纤维化和肝癌的风险。

In order to evaluate the risk of parasite-derived miRNAs in extracellular membrane vesicles of Clonorchis sinensis in cross-species regulation of host genes,the miRBase database was used to screen the mature sequences of parasite-derived miRNAs shared by Clonorchis sinensis(C.sinensis)extracellular vesicles and the infected host cells.miRanda software was used to predict the target genes of the top 10 miRNAs in extracellular membrane vesicles,and the top 10 target genes of each miRNAs score were selected as candidate target genes.NCBI and Bing search tools were used to search the functions of the candidate target genes of miRNAs,and GO functional annotation and KECG enrichment analysis were used for bioinformatics analysis of target genes.The results showed that 10 miRNAs in the extracellular vesicles of C.sinensis corresponded to a total of 8128 host-related target genes:.Twelve candidate target genes had no relevant functional reports;twelve candidate target genes were related to liver function,and the remaining candidate target genes played important roles in cancer,signal transduction,structural skeleton,proliferation and dfferentiation,and migration.The candidate target genes Taf0 and Onecut2 were related to the development of liver and hepatobiliary duct.Gngl and Hhip were involved in the mitogen-activated protein kinase(MAPK)and Hedgehog signaling pathways associated with fibrosis,respectively.These results indicated that insect-derived miRNAs had the potential to target host cells and participate in the development of host liver fibrosis and liver cancer.