Differential expression of circular RNA in patients with chronic HBV infection of different stages and related bioinformatic analysis / 中华临床感染病杂志

ABSTRACT

Objective To investigate the differential expression of circular RNA ( circRNA ) in patients with chronic HBV infection of different stages.Methods Seven patients with chronic HBV infection admitted in Taizhou People's Hospital from October 2014 to October 2015 were enrolled, including 4 with chronic hepatitis B ( CHB ) and 3 chronic HBV carriers;3 healthy subjects served as controls. Peripheral blood mononuclear cells (PBMCs) were separated,and the expression of circRNA molecules in PBMCs were detected by new generation of circRNA microarray and validated by fluorescent quantitative PCR.The interaction sites between circRNA and miRNA were predicted with Arraystar miRNA target prediction software.Target genes regulated by the circRNA related to miRNA were analyzed by Gene oncology (Go) and Kyoto encyclopedia of genes and genomes (KEGG) analysis.SPSS 17.0 software was used for statistical analysis.Results Compared with the healthy controls , 137 circRNA molecules of differential expression were found in patients with chronic hepatitis B , of which 89 were up-regulated and 48 were down-regulated; while 444 circRNA molecules of differential expression , of which 130 were up-regulated (>5 fold in 34 ) and 314 down-regulated , were found in chronic HBV carriers.Compared with chronic HBV carriers , 1041 circRNA molecules of differential expression were found in CHB patients , including 663 up-regulated and 378 down-regulated (>5 fold in 54).There were many miRNA responsive elements which complementary with seed regions on miRNA in different circRNA molecules.Target gene analysis demonstrated that 533 target genes regulated by hsa_circ_0038646 were related to miRNAs , 249 target genes found in hsa_circ_0087354 were related to microRNAs.GO analysis showed that function of target genes regulated by hsa_circ_0038646 related to miRNA mainly enriched in activin binding.Function of target genes regulated by hsa_circ_0087354 related to miRNA mainly enriched in armadillo repeat domain binding.KEGG analysis showed that hsa_circ_0038646 molecules related to miRNA mainly involved in T cell receptor , estrogen receptor signaling pathway and so on.Hsa_circ_0087354 molecules related to miRNA mainly involved in adherens junction , MAPK signaling pathway and so on. Conclusion There are differential expressions of circRNA in patients at different clinical stages of chronic HBV infection , which might be involved in immune regulation of chronic HBV infection through the regulation of multiple target genes and signaling pathways.