Introduction:
To identify circular RNA (circRNA) expression profiles in the blood of preeclampsia (PE) and healthy pregnant women, and further clarify the possible mechanisms of circRNAs involved in the pathogenesis of PE.

Material and methods:
Whole blood samples were collected from 5 paired PE and healthy pregnant women. The differentially expressed circRNAs (DE-circ­RNAs) were investigated using high-throughput sequencing. Bioinformatics was performed to evaluate the sequencing results and obtain insights into possible mechanisms, such as gene ontology (GO) and KEGG pathway analyses. Then, six DE-circRNAs were chosen and validated by quantitative real-time PCR (RT-qPCR) in an enlarged sample size. Their diagnostic values were analyzed by the receiver operating characteristic (ROC) curve. Establishment and analysis of the circRNA-miRNA-mRNA network were performed for the validated DE-circRNAs.

Results:
A total of 139 DE-circRNAs between PE and controls were revealed. Of them, 18 circRNAs were upregulated, and 31 circRNAs were downregulated (fold change > 2 and p-value < 0.05). Three circRNAs (has-circ-0007717, has-circ-0006460, and has-circ-0093055) were higher in both blood of early-onset and late-onset PE patients. The ROC analysis showed that the area under the curve values of has-circ-0007717, has-circ-0006460, and has-circ-0093055 were 0.64 (p = 0.11), 0.72 (p = 0.01), and 0.72 (p = 0.01), respectively. The circRNA-miRNA-mRNA competing for the endogenous RNA (ceRNA) network comprised 2 circRNAs, 154 miRNAs, and 6 mRNAs. KEGG analysis of these mRNAs included immune response-related pathways and cellular senescence.

Conclusions:
The CeRNA regulatory network indicated that DE-circRNAs might participate in the processes of the cell immune response.