Expression profiles and potential clinical significance of circular RNAs in peripheral neutrophils of patients with intracranial atherosclerotic stenosis.

BACKGROUND

Expression profiles and clinical significance of circular RNAs (circRNAs) in intracranial atherosclerotic stenosis (ICAS) patients have not been investigated yet.

MATERIALS AND METHODS

A circRNA microarray was employed to identify differentially expressed circRNAs (DEcircRNAs) in peripheral neutrophils of ICAS patients. The levels of upregulated hsa-circRNA-087631/hsa-circRNA-101141 and downregulated hsa-circRNA-100914/hsa-circRNA-001082 were verified using quantitative real-time polymerase chain reaction (qRT-PCR). In addition, we compared the levels of those four DEcircRNAs before endovascular treatment (pre-E) and 24 h after endovascular treatment (post-E) and between patients with adverse event and severe adverse event (AE/SAE) and those without. Their area under the curve from the receiver operating characteristic (ROC) curve was calculated as well. Bioinformatic analyses of DEcircRNAs host genes and targeted genes in DEcircRNA-miRNA-mRNA regulatory network were further performed.

RESULTS

A total of 70 circRNAs were identified as differentially expressed in patients with ICAS; of these, 7 were upregulated and 63 were downregulated. qRT-PCR-based validation results of the four DEcircRNAs corresponded with the microarray data. The upregulated hsa-circRNA-087631 and hsa-circRNA-101141 were significantly downregulated 24 h post-E; moreover, they were significantly increased in patients with perioperative AE/SAE compared to those without AE/SAE. ROC analysis further supported their potential to be exploited as diagnostic biomarkers for ICAS. The validated DEcircRNA-miRNA-mRNA regulatory network and further bioinformatic analysis supported the core roles of hsa-circRNA-101141 in regulating target genes mainly related to actin or microtubule-based process.

CONCLUSIONS

DEcircRNAs in peripheral neutrophils could serve as biomarkers for the diagnostic and AE prediction in ICAS patients receiving endovascular treatment. Moreover, these DEcircRNAs, especially hsa-circRNA-101141-hsa-miRNA-181d axis, might participate in the pathogenesis of ICAS by acting on actin or microtubule-based cytoskeleton organization processes in neutrophils.

TRIAL REGISTRATION

The CRTICAS study has been registered previously in the ClinicalTrial.gov database (NCT01994161).