Lina Wei1, Chunlei Xin2, Wenjuan Wang3, Cuifang Hao4. 1. 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. 2. Department of Hematology, Jining No. 1 People's Hospital, Jining, Shandong 272011, PR China. 3. Department of Reproductive Medical, The Affiliated Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, PR China. 4. Department of Reproductive Medical, The Affiliated Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, PR China. Electronic address: cuifang-hao@163.com.
Abstract
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.
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 PCOSpatients 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.
Authors: Zulazmi Sutaji; Marjanu Hikmah Elias; Mohd Faizal Ahmad; Abdul Kadir Abdul Karim; Muhammad Azrai Abu Journal: Front Endocrinol (Lausanne) Date: 2022-07-01 Impact factor: 6.055
Authors: ShanHu Gao; Fei Long; Zheng Jiang; Jun Shi; DongXue Ma; Yang Yang; Jin Bai; Ting-Li Han Journal: Front Physiol Date: 2022-09-20 Impact factor: 4.755