Microarray Expression Profile of Circular RNAs in Plasma from Primary Biliary Cholangitis Patients

Abstract

Background/Aims: Circular RNAs (circRNAs) play a crucial role in the occurrence of several diseases, including autoimmune diseases. However, their role in primary biliary cholangitis (PBC) remains unclear. Here, we aimed to determine the circRNA expression profile in plasma from PBC patients and further explore the value of circRNA in diagnosing PBC. Methods: CircRNA microarrays were used to determine circRNA expression profiles in plasma samples from 6 PBC patients and 6 healthy controls. Statistical analyses identified differentially expressed circRNAs, and these circRNAs were verified by qRT-PCR in 29 PBC patients and 30 healthy controls. MicroRNA (miRNA) target prediction software identified putative miRNA response elements (MREs), which were used to construct a map of circRNA-miRNA interactions for the differentially expressed circRNAs. Results: Our results indicated that there were 18 up-regulated and 4 down-regulated circular RNAs in the plasma from PBC patients compared with that from healthy individuals. Among the differentially expressed circRNAs, hsa_circ_402458 (P=0.0033), hsa_circ_087631 and hsa_circ_406329 (P=0.0185) were up-regulated, and hsa_circ_407176 (P=0.0066) and hsa_circ_082319 were down-regulated in the PBC group versus the healthy group as demonstrated by qRT-PCR. In particular, hsa_circ_402458 was significantly higher in PBC patients not receiving UDCA treatment than in PBC patients receiving UDCA treatment (P=0.0338). The area under the receiver operating characteristic curve for hsa_circ_402458 for diagnosing PBC was 0.710 (P=0.005). For hsa_circ_402458, two putative miRNA targets, hsa-miR-522-3p and hsa-miR-943, were predicted. Conclusions: circRNA dysregulation may play a role in PBC pathogenesis, and hsa_circ_402458 shows promise as a candidate biomarker for PBC.

Circular RNAs in immune responses and immune diseases

“…Zheng et al performed a circRNA microarray analysis of plasma from patients with PBC and healthy individuals and identified 18 upregulated and 4 downregulated circRNAs that were possibly associated with PBC. Subsequently, among the 18 elevated circRNAs, hsa_circ_402458 was demonstrated to be a biomarker of PBC 123. Two miRNAs, i.e., miR-522 and miR-943, are putative biotargets of hsa_circ_402458 .…”

Deep RNA Sequencing Reveals a Repertoire of Human Fibroblast Circular RNAs Associated with Cellular Responses to Herpes Simplex Virus 1 Infection

“…They are formed from pre-mRNAs by a back-splicing event that refers to the alternative circularization of the 5' end of the upstream exon to the 3' end of the downstream exon in order to produce a covalently closed loop [3,4]. The covalently closed loop structures confer high resistance to RNA exonuclease or RNase R, rendering them more durability as compared to linear RNAs.…”

Circular RNA Expression Profiles in Plasma from Patients with Heart Failure Related to Platelet Activity

“…CircRNAs can modulate alternative splicing, transcription, and the expression of parental genes; one of the regulatory pathways involves microRNA (miRNA) sponges [23][24][25]. Differential circRNA profiles occur in patients with nonsmall cell lung cancer, primary biliary cholangitis, papillary thyroid carcinoma, and hypertension; certain circRNAs may serve as potential biomarkers in disease diagnosis [26][27][28]. A total of 15,318 circRNAs have been identified in the human heart, and highly expressed circRNA correspond to key cardiac genes, including titin, ryanodine receptor 2, and Duchenne muscular dystrophy [29].…”