Characterization of circular RNA expression profiles in cumulus cells from patients with polycystic ovary syndrome

Abstract

Objective: To determine aberrant circular RNA (circRNA) expression profiles in cumulus cells from polycystic ovarian syndrome (PCOS) patients and identify their potential biological functions.

Design: Circular RNAs microarray analysis of human tissue.

Setting: University hospital.

Patient(s): A total of 40 women, including 20 PCOS patients and 20 non-PCOS patients.

Intervention(s): None.

Main outcome measure(s): A circRNA microarray containing probes that interrogate 21,442 human circRNAs to investigate differentially expressed circRNAs in cumulus cells, with potential target genes of significantly changed circRNAs and biological functions measured by microRNA support vector regression (mirSVR) and gene ontology (GO) analysis, with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis.

Result(s): A total of 1,032 circRNAs were identified that were differentially expressed in PCOS cumulus cells, including 311 circRNAs increase and 721 circRNAs decrease (fold change ≥2). Four aberrantly expressed circRNAs reached a statistically significant result after Bonferroni correction (with Bonferroni correction, only circRNAs for which P < .05/21,442 = 2.3 × 10^-6 were considered statistically significant). Further analysis showed that aberrantly expressed circRNAs harbored microRNA binding sites, and some microRNAs were associated with PCOS. The GO and KEGG biological pathway analysis indicated that the genes with protein binding, mitotic nuclear envelope disassembly and metabolic pathways were statistically significantly enriched.

Conclusion(s): Our data suggest that the aberrantly expressed circRNAs and their targeted genes might be associated with PCOS, providing new clues to find key diagnostic and therapeutic molecular biomarkers for PCOS patients.

Keywords: Cumulus cells; circular RNAs; microarray; polycystic ovary syndrome.