Wei Lina, Xin Chunlei, Wang Wenjuan, Hao Cuifang

Department of Reproductive Medical, The Affiliated Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, PR China; Department of Reproductive Medical, Jining No. 1 People's Hospital, Jining, Shandong 272011, PR China.| Department of Hematology, Jining No. 1 People's Hospital, Jining, Shandong 272011, PR China.| Department of Reproductive Medical, The Affiliated Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, PR China.| Department of Reproductive Medical, The Affiliated Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, PR China. Electronic address: cuifang-hao@163.com.

Gene. 2018 Jun 30;661:85-94. doi: 10.1016/j.gene.2018.03.079. Epub 2018 Mar 28.

PURPOSE: This study aimed to screen key genes and pathways involved in obese polycystic ovary syndrome (PCOS), and predict drugs for treatment of obese PCOS via bioinformatics approaches.
METHODS: Microarray dataset GSE10946 were downloaded from the Gene Expression Omnibus database, including 7 cumulus cell samples from obese PCOS patients and 6 lean control samples. Differentially expressed genes (DEGs) between obese PCOS and controls were obtained using Bayesian test after data preprocessing, followed by functional enrichment analyses for DEGs. Besides, protein-protein interaction (PPI) network and sub-network analyses were performed. Furthermore, drug prediction was carried out based on the DEGs.
RESULTS: A total of 793 DEGs were identified in PCOS compared with control, including 352 up-regulated and 441 down-regulated DEGs. Specifically, upregulated RNA polymerase I subunit B (POLR1B), DNA polymerase epsilon 3, accessory subunit (POLE3), and DNA polymerase delta 3, accessory subunit (POLD3) were enriched in pathway of pyrimidine metabolism associated with obesity and PCOS, and 5-hydroxytryptamine receptor 2C (HTR2C) was enriched calcium signaling pathway. Additionally, 10 significant potential drugs, such as spironolactone targeting androgen receptor (AR), trimipramine targeting adrenoceptor beta 2 (ADRB2), and L-ornithine targeting ornithine decarboxylase antizyme 3 (OAZ3), were obtained.
CONCLUSIONS: In conclusion, POLR1B, POLE3, POLD3, and HTR2C might play important roles in obese PCOS via involvement of pyrimidine metabolism and calcium signaling pathway. Moreover, AR, ADRB2, and OAZ3 might be targets of spironolactone, trimipramine, and L-ornithine in the treatment of obese PCOS.