Tempol modulates lncRNA-miRNA-mRNA ceRNA networks in ovaries of DHEA induced PCOS rats

Polycystic ovary syndrome (PCOS) is one of the most common endocrine and metabolic disorders in reproductive age women. Our previous results demonstrated that tempol was able to ameliorate PCOS phenotype in rats. However, the exact pathophysiological effect of tempol on PCOS remains largely unknown. To extend this research, deep RNA-sequencing was performed to investigate the long noncoding RNA (lncRNA) associated ceRNA mechanisms in the ovarian tissues of control rats, dehydropiandrosterone (DHEA) induced PCOS rats and tempol treated PCOS rats. Our results identified total 164, 79, and 914 significantly dysregulated lncRNAs, miRNAs, and mRNAs in three groups, respectively. The total of 7 lncRNAs, 8 mRNAs and 5 miRNAs were involved in lncRNA-associated ceRNA networks were constructed. Among them, mRNAs including C1qtnf1, Dipk2a, IL4r and lncRNAs including MSTRG.16751.2, MSTRG.8065.2 had high RNA connectivity in the ceRNA network, which also showed significant alterations in these three groups by using qPCR validation. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that the involvement of the identified ceRNA networks in regulating the development of PCOS from distinct origins, such as metabolic pathway, immune cell differentiation. The study presents the first systematic dissection of lncRNA-associated ceRNA profiles in tempol treated PCOS rats. The identified ceRNA networks could provide insights that help facilitate PCOS diagnosis and treatment.