Novel Circular RNA Expression In The Cumulus Cells And Its Potential Significance In The Pathogenesis Of Polycystic Ovary Syndrome

Objective: This study aimed to detect the novel expression of circRNAs in the cumulus cells?CCs?of polycystic ovary syndrome?PCOS?patients and their potential significance in the pathogenesis of PCOS.Methods: circRNAs in the CCs from 6 PCOS patients and 6 normal control individuals were collected for microarray analysis,and an independent cohort study including 25 PCOS patients and 25 normal control individuals was conducted to validate the circRNA microarray results using quantitative real-time polymerase chain reaction?qRT-PCR?.Spearman's rank correlation and receiver operating characteristic?ROC?were performed to delineate the potential correlation between novel circRNAs and patients' clinical characteristics and their potential efficacy for the diagnosis of PCOS.Bioinformatics analysis was applied to investigate the potential roles of circRNAs in the pathogenesis of PCOS.Results: A total of 286 circRNAs?167 upregulated and 119 downregulated?were identified by microarray that were differentially expressed between the PCOS and non-PCOS groups.KEGG pathway revealed that the dysregulated circRNAs were potentially involved in cell cycle,oocyte meiosis and progesterone-mediated oocyte maturation.After qRT-PCR validation,the expression levels of hsa_circ₀043533?p<0.05?and hsa_circ₀043532?p<0.01?were significantly higher in the PCOS group,while the expression level of hsa_circ₀097636?p<0.01?was prominently lower versus the non-PCOS group.The expression of hsa_circ₀118530?p=0.4157?,hsa_circ₀020491?p=0.1536?and hsa_circ₀074576?p=0.4440?showed no significant differences between two groups.Spearman's rank correlation indicated that the serum testosterone?T?level positively correlated with the expression of hsa_circ₀043533 and hsa_circ₀097636 in the PCOS group.The ROC curve analysis found thatthe combination of hsa_circ₀097636 and T resulted in a larger area under the curve?AUC??0.893?compared with each circRNA alone?0.709,0.738 and 0.718 for hsa_circ₀043533,hsa_circ₀097636 and hsa_circ₀043532,respectively?.Cytoscape network indicated that the dysregulated circRNAs may contribute to the pathogenesis of PCOS by regulating the expression of DGKI,PCYT1 B,FOXO3 and CCNB1 through targeting miR-30 c,miR-125 b and miR-132,respectively.Conclusions: The expression of circRNAs in CCs was significantly different between PCOS and normal control individuals.We validated three circRNAs,which could lead to a better understanding of disease pathogenesis and the development of effective therapeutic interventions for PCOS patients.