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.
Gene. 2018 Jun 30;661:85-94. doi: 10.1016/j.gene.2018.03.079. Epub 2018 Mar 28.
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.
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.
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.
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.
本研究旨在通过生物信息学方法筛选肥胖型多囊卵巢综合征（PCOS）相关的关键基因和通路，并预测治疗肥胖型 PCOS 的药物。
从基因表达综合数据库中下载微阵列数据集 GSE10946，包括 7 例肥胖型 PCOS 患者的卵丘细胞样本和 6 例瘦对照样本。对数据预处理后使用贝叶斯检验获得肥胖型 PCOS 与对照组之间的差异表达基因（DEGs），并对 DEGs 进行功能富集分析。此外，还进行了蛋白质-蛋白质相互作用（PPI）网络和子网络分析。最后，基于 DEGs 进行药物预测。
与对照组相比，PCOS 中共有 793 个 DEGs，包括 352 个上调和 441 个下调 DEGs。具体而言，上调的 RNA 聚合酶 I 亚基 B（POLR1B）、DNA 聚合酶 epsilon 3 辅助亚基（POLE3）、DNA 聚合酶 delta 3 辅助亚基（POLD3）在与肥胖和 PCOS 相关的嘧啶代谢途径中富集，5-羟色胺受体 2C（HTR2C）在钙信号通路中富集。此外，还获得了 10 种潜在的重要药物，如针对雄激素受体（AR）的螺内酯、针对肾上腺素能受体β 2（ADRB2）的曲米帕明和针对鸟氨酸脱羧酶抗酶 3（OAZ3）的 L-鸟氨酸。
总之，POLR1B、POLE3、POLD3 和 HTR2C 可能通过参与嘧啶代谢和钙信号通路在肥胖型 PCOS 中发挥重要作用。此外，AR、ADRB2 和 OAZ3 可能是螺内酯、曲米帕明和 L-鸟氨酸治疗肥胖型 PCOS 的靶点。
