MicroRNA Profile In Peripheral Blood T Cells Of Primary Biliary Cirrhosis Patients And Its Mechanism Of Action

To explore the RNA mechanism of PBC,we focus on the microRNA(miRNA) profile in the peripheral blood T cells of PBC and study on the action mechanism of miRNA in PBC.We first explored changes in the miRNA expression profile in the peripheral blood T cells of PBC patients by microarray and real-time PCR,then investigated the regulatory effects of some miRNA abnormally expressed in PBC on the proliferation of PDC-E2-specific autoreactive T cells.Subsequently,the effects of miRNA on the pathology of PBC disease were studied in animal models.Finally,miRNA target genes were predicted by bioinformatics and the effect of miRNA on the function of target genes was determined.The results showed that Twenty-three miRNA in the array were found to be expressed in low levels and two miRNA had high levels of expression in the peripheral blood T cells of patients with PBC.The proliferation and secretion of IFN-γ,TNF-αof autoantigen-specific T cells were inhibited by miR-let-7b,miR-17-5p,miR-20a,miR-346 and promoted by miR-129,miR-451.Injecting poly I:C into syngenic wild-type mice produced PBC-like pathological changes,which were alleviated following injection of Ad-miR-17-5p or Ad-miR-346.The target gene of miR-17-5p,miR-346 is TNFRSF21, BCL-6.The interaction sites are TNFRSF21 3' UTR 335-342,BCL-6 3' UTR 576-583 and 893-900.