Genome-wide Analysis of Circular RNAs and Validation of hsa_circ_0086354 As a Promising Biomarker for Early Diagnosis of Cerebral Palsy

Abstract

Background: Cerebral palsy (CP) is a spectrum of non-progressive motor disorders caused by brain injury during fetal or postnatal periods. Current diagnosis of CP mainly relies on neuroimaging and motor assessment. Here, we aimed to explore novel biomarkers for early diagnosis of CP. Methods: Blood plasma from five CP children and their healthy twin brothers/sisters was analyzed by gene microarray to screen out differentially expressed RNAs. Selected differentially expressed circular RNAs (circRNAs) were further validated using quantitative real-time PCR. Receiver operating characteristic (ROC) curve analysis was used to evaluate the value of using hsa_circ_0086354 as a biomarker of CP.Results: 43 up-regulated circRNAs and 2 down-regulated circRNAs were obtained by difference analysis (fold change>2, p<0.05), among which five circRNAs related to neuron differentiation and neurogenesis were chosen for further validation. Additional 30 pairs of CP children and healthy controls were recruited and five selected circRNAs were further detected, showing that hsa_circ_0086354 was significantly down-regulated in CP plasma compared with control, which was highly in accord with microarray analysis. ROC curve analysis showed that the area under curve (AUC) to discriminate CP children and healthy controls using hsa_circ_0086354 was 0.967, the sensitivity was 0.833 and the specificity was 0.966. Moreover, hsa_circ_0086354 was predicted as a competitive endogenous RNA for miR-181a, miR-4741 and miR-4656, and much literature evidence suggested that miR-181a may be a key target of hsa_circ_0086354 to regulate neuronal survival and neuronal differentiation. Conclusion: Hsa_circ_0086354 was significantly down-regulated in blood plasma of CP children, which may be a novel competent biomarker for early diagnosis of CP.