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

Cell Physiol Biochem. 2017;44(4):1271-1281. doi: 10.1159/000485487. Epub 2017 Nov 29.

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.

Keywords: CircRNAs; Hsa_circ_402458; PBC.

MeSH terms

  • Area Under Curve
  • Base Sequence
  • Bile Ducts
  • Biomarkers / blood
  • Case-Control Studies
  • Cholangitis / metabolism
  • Cholangitis / pathology
  • Cluster Analysis
  • Humans
  • MicroRNAs / chemistry
  • MicroRNAs / metabolism
  • Nucleic Acid Hybridization
  • Oligonucleotide Array Sequence Analysis
  • RNA / blood*
  • RNA / chemistry
  • RNA, Circular
  • ROC Curve
  • Real-Time Polymerase Chain Reaction
  • Sequence Alignment
  • Transcriptome

Substances

  • Biomarkers
  • MicroRNAs
  • RNA, Circular
  • RNA