has_circ_0009096和has_circ_00083234在胆道闭锁肝组织中的表达及其机制的研究

Expression of hsa_circ_0009096 and hsa_circ_0083234 in biliary atresia and its mechanism

目的分析胆道闭锁患者肝组织中hascirc0009096和hascirc00083234的表达差异及其作用机制。方法通过RT-qPCR检测了15例BA组及其对照组肝组织中hascirc0009096和hascirc00083234的表达水平;通过生物信息技术预测了能够与它们结合的miRNA及其下游靶基因,并进行KEGG信号通路富集分析以阐明BA的潜在发病机制。结果hascirc0009096在BA组中的相对表达水平高于CC组(P<0.0001);hascirc00083234在BA组中的表达水平下调(P=0.0037)。通过circRNA预测的靶miRNA与BA相关的miRNA集相交,我们获得了4个miRNA(hsa-miR-145-5p,hsa-miR-222-3p,hsa-miR-221-3p和hsa-miR-432-5p)。基于这2个circRNA和4个miRNA,建立了circRNA-miRNA调控网络。根据miRNA下游基因进行KEGG信号通路富集分析,发现了Hippo,TGF-β,Adherens junction,Focal adhesion,ECM-receptor interaction以及多能干细胞调节等多条信号通路可能与BA的发病机制相关。结论hascirc0009096和hascirc00083234在BA肝组织中表达失调,并可能参与BA的疾病进展。因此,hascirc0009096和hascirc00083234可作为BA诊断的候选指标,而circRNA-miR通路的研究可能为探索BA的发病机制提供新的思路。

Objective:Objective to explore the expression difference of hascirc0009096 and hascirc00083234 in liver tissue of patients with biliary atresia and its mechanism.Methods:The expression levels of hascirc0009096 and hascirc00083234 in 15 cases of Ba group and its control group were detected by RT-qPCR.miRNAs and their downstream target genes were predicted by bioinformatics technology,and KEGG signaling pathway enrichment analysis was carried out to elucidate the potential pathogenesis of BA.Results:The relative expression level of hascirc0009096 in BA group was higher than that in CC group(P<0.0001),and the expression level of hascirc00083234 in BA group was down regulated(P=0.0037).Four miRNAs were obtained by crossing the predicted target miRNAs with BA related miRNAs(hsa-miR-145-5p,hsa-miR-222-3p,hsa-miR-221-3p和hsa-miR-432-5p).Based on these two circRNAs and four miRNAs,a circRNA-miRNA regulatory network was established.KEGG signaling pathway enrichment analysis based on miRNA downstream genes revealed that hippo,TGF-β,adhesions junction,focal adhesion,ECM receptor interaction and regulating pluripotency of stem cells may be related to the pathogenesis of BA.Conclusion:Dysregulation of has circ 0009096 and has circ 00083234 may be involved in the progression of BA.Therefore,has circ 0009096 and has circ 00083234 can be used as a candidate marker for BA diagnosis,and the study of circRNA-miRNA may provide a new way for exploring the pathogenesis of BA.