Several critical genes and microRNAs associated with the development of polycystic ovary syndrome
| Autor: | Juan Ji, Wei Wang, Yuqin Zhao, Yong Tan, Dandan Hong, Junjie Gu, Qian Guo, Qing-ling Ren, Jin Li |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Endocrinology Diabetes and Metabolism 030209 endocrinology & metabolism Biology 03 medical and health sciences 0302 clinical medicine Endocrinology Downregulation and upregulation Gene expression microRNA Humans Gene Regulatory Networks Genetic Predisposition to Disease RNA Messenger Gene Cells Cultured Genetic Association Studies Granulosa Cells Microarray analysis techniques Competing endogenous RNA Gene Expression Profiling General Medicine Microarray Analysis Polycystic ovary Cell biology MicroRNAs Case-Control Studies 030220 oncology & carcinogenesis Female Leukocyte Transendothelial Migration Pathway Polycystic Ovary Syndrome |
| Zdroj: | Annales d'Endocrinologie. 81:18-27 |
| ISSN: | 0003-4266 |
| DOI: | 10.1016/j.ando.2019.10.002 |
| Popis: | Background We aimed to identify key genes and microRNAs (miRNAs) associated with the development of polycystic ovary syndrome (PCOS). Methods GSE84376 mRNA microarray data (15 PCOS granulosa cells and 13 control granulosa cells) and GSE34526 mRNA microarray data (7 PCOS granulosa cells and 3 control granulosa cells) were downloaded from the Gene Expression Omnibus (GEO) database. First, differentially expressed gene (DEG) analysis, gene set enrichment analysis (GSEA) for differentially expressed mRNAs, and protein–protein interaction (PPI) network analysis were conducted. Next, miRNA-target genes were analyzed and functions predicted, and a competing endogenous RNA (ceRNA) network was constructed. Finally, the relationship between miR-486-5p and PRELID2 was experimentally validated. Results Spleen tyrosine kinase (SYK), major histocompatibility complex, class II, DR alpha (HLA-DRA), and interleukin 10 (IL-10) were important nodes in the PPI network. Interestingly, HLA-DRA was significantly enriched in phagosomes mediated by Staphylococcus aureus infection, and in IL-10 enriched during S. aureus infection. One miRNA (miR-486-5p) and a single target gene (PRELID2) were obtained from the ceRNA network. Further experiments showed that miR-486-5p is upregulated and PRELID2 is downregulated in PCOS patient granulosa cells, and that miR-486-5p targets the PRELID2 3′UTR. Topological property analysis showed that hsa-miR-4687-5p downregulation and hsa-miR-4651 upregulation determined the levels of most mRNAs. Levels of the hsa-miR-4651 target gene were significantly enriched in the leukocyte transendothelial migration pathway. Conclusions Our results suggest that HLA-DRA and IL-10 may contribute to PCOS progression via phagosome enriched by S. aureus infection, while miR-486-5p may be implicated in follicular development in PCOS by targeting PRELID2. Besides, miR-4651 may be involved in inflammation via leukocyte transendothelial migration, by regulating its target gene. These findings may indicate new directions and constitute a breakthrough in studying the pathophysiology of PCOS. |
| Databáze: | OpenAIRE |
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