Profiles of Circular RNAs in Human Placenta and Their Potential Roles Related to Preeclampsia

To identify the profiles of circular RNAs (circRNAs) in human placental tissues and to explore the potential roles of dysregulated circRNAs in the pathological genesis of preeclampsia, expression profiles of circRNAs in human placentas were performed in this study. Utilizing high-throughput technology, based on fold changes and P values, 300 circRNAs that are differentially expressed between preeclampsia and normal placental tissues were identified. Among them, hg38_circ_0014736 and hsa_circ_0015382 were validated as significantly upregulated by real-time quantitative PCR with divergent primers. At the same time, hsa_circ_0007121 was significantly downregulated. GO analysis revealed that the three altered circRNAs had a relationship with transcription regulation, proliferation, protein binding, and response to hypoxia. KEGG analysis yielded that apoptosis, Wnt signaling, and HIF-1 pathways were significantly enriched. Interestingly, hsa_circ_0007121 was found to be expressed differently in plasma between preeclampsia and normal pregnancy and this difference could be detected before 20 gestational weeks. Besides, addition receiver operating characteristic (ROC) curve analysis showed that the area under the ROC curve of hsa_circ_0007121 reached 0.72 ([0.59-0.85], P = 0.004) with a sensitivity of 0.77 and specificity of 0.70. Collectively, this study demonstrates the existence of dysregulated circRNAs in the placenta of preeclampsia patients and annotates their potential roles in the pathogenesis of the disease. Encouragingly, hsa_circ_0007121 was found to be a potential noninvasive biomarker for the prediction of preeclampsia.