MicroRNA-223 and microRNA-21 in peripheral blood B cells associated with progression of primary biliary cholangitis patients

Abstract

Recently, there is ample evidence suggesting the important role of microRNAs (miRNAs) in autoimmune diseases via modulating B cells function. Primary biliary cholangitis (PBC) is a progressive immune-mediated liver disease with unclear pathogenic mechanism. Whether the miRNA in peripheral B cells of PBC involve the mechanisms of pathology and progression is not known. The present study explores miRNA deregulation in peripheral B-cell of PBC from stage I to IV and healthy controls. Peripheral B cells were obtained from 72 PBC patients (stage I, n = 17; stage II, n = 23; stage III, n = 16; stage IV, n = 16) and 15 healthy controls. Initially, in a discovery study, miRNA array analysis was performed, subsequently, in a validation study, quantitative PCR was used to investigate miRNA expression profile in B cells of PBS patients compared to healthy controls. Based on bioinformatics analysis, we identified the potential biological processes and significant signaling pathways affected by these microRNAs, and generated the microRNA–gene network. The discovery study identified 558 miRNAs differentially expressed in B cells of PBC patients compared to controls. Interestingly, among all differentially expressed miRNAs, hsa-miR-223-3p and hsa-miR-21-5p were the only miRNAs that showed consistent and significant down-regulation from stage I to stage III of PBC. Bioinformatics showed that potential target genes of both miRNAs involved in migration, cell differentiation, apoptosis, and signal transduction pathways. In conclusion, our results suggest that the expression profiles of miRNA in peripheral B cells of PBC patients are closely associated with the disease progression, especially the down-regulation of hsa-miR-223-3p and hsa-miR-21-5p. Taken together, our study offers novel perspectives on the role of miRNAs in PBC pathogenesis.

Enhanced expression of miR-21 and miR-150 is a feature of anti-mitochondrial antibody-negative primary biliary cholangitis

“…Hence, it is not surprising that increased miR-21 expression is closely associated with the maintenance of autoreactive immunity (Stagakis et al 2011). In dominant-negative TGF-β receptor II mice, which spontaneously develop an autoimmune cholangitis similar to human PBC the T cell dysregulation is associated with upregulation of the key inflammatory miR-21 (Ando et al 2013), and in close relevance to the present study, miR-21 has showed consistent and significant down-regulation in B cells of PBC patients from stage I to stage III of PBC (Wang et al 2017). The biological significance of this finding in a presumably T-cell mediated autoimmune liver diseases and its pathophysiological connotations in AMA positive versus AMA negative patients remains elusive.…”

Biomarkers for primary biliary cholangitis: current perspectives

“…Although more than 500 miRNAs were differentially expressed in patients, only hsa-miR-223-3p and hsa-miR-21-5p showed consistent downregulation from stage I to stage III suggesting that they are related to disease progression. 51 …”

MiR-29c-3p and MiR-223-3p Regulate the Proliferation and Drug Resistance of OSCC by Targeting ANGPTL4

“…The expression of miR-223-3p is abnormal in a variety of diseases. For example, the expression of miR-223-3p downregulated in clear cell renal cell carcinoma [28] , ossi ed broma [29] , and primary biliary cholangitis [30] , suggesting that miR-223-3p may be involved in the occurrence and development of a variety of diseases.…”