Bioinformatics identification of microRNAs involved in�polycystic ovary syndrome based on microarray data

Abstract

Polycystic ovary syndrome (PCOS) is the most common endocrine disease in women of reproductive age. MicroRNAs (miRNAs or miRs) serve important roles in the physiological and pathological process of PCOS. To identify PCOS-associated miRNAs, the dataset GSE84376 was extracted from the Gene Expression Omnibus database. Differentially expressed miRNAs (DE-miRNAs) were obtained from Gene-Cloud Biotechnology Information and potential target genes were predicted using TargetScan, DIANA-microT-CDS, miRDB and miRTarBase tools. Gene Ontology enrichment analysis was performed using Metascape and a protein-protein interaction network was constructed using Cytoscape. Transcription factors were obtained from FunRich. DE-miRNAs were verified by reverse transcription-quantitative PCR. At the screening phase, there were seven DE-miRNAs in the PCOS group not present in the control group. In total, 935 target genes were identified, which are involved in the development and maturation of oocytes. Mitogen-activated protein kinase 1, phosphatase and tensin homolog, cAMP responsive element binding protein 1, signal transducer and activator of transcription 3, interferon γ, Fms-related tyrosine kinase 1, transcription factor p65, insulin receptor substrate 1, DnaJ homolog superfamily C member 10 and casein kinase 2 α 1 were identified as the top 10 hub genes in the protein-protein interaction network. Specificity protein 1 was the most enriched transcription factor. At the validation phase, the levels of Homo sapiens (hsa)-miR-3188 and hsa-miR-3135b were significantly higher in the PCOS group than in the control group. In addition, the expression level of hsa-miR-3135b was significantly correlated with the number of oocytes retrieved, the fertilization rate and the cleavage rate (P<0.05). The present bioinformatics study on miRNAs may offer a novel understanding of the mechanism of PCOS, and may serve to identify novel miRNA therapeutic targets.

Identification of Crucial lncRNAs, miRNAs, mRNAs, and Potential Therapeutic Compounds for Polycystic Ovary Syndrome by Bioinformatics Analysis

“…Similarly, two miRNA expression profile datasets were used. Although some key miRNAs and mRNAs identified in the previous studies (miR-3135, miR-3188 [ 16 , 18 ], and miR-486 [ 17 ]; aquaporin 9, free fatty acid receptor 2, and S100 calcium binding protein A8 [ 15 ]) were also found in our study, they were not the focus because they were only identified in one dataset (miRNA, GSE84376) or not included in preserved modules. More interestingly, we, for the first time, integrated the DEL-DEG and DEL-DEM-DEG data to construct the coexpression and ceRNA network.…”

“…Although previous studies have attempted to reveal the molecular mechanisms of PCOS by using high-throughput microarray or sequencing data [ 15 – 19 ], all of them focused on the single dataset (mRNA: GSE95728 [ 15 ], miRNA: GSE84376 [ 16 , 18 ], miRNA: GSE84376 and mRNA: GSE34526 [ 17 ], and mRNA: GSE34526 [ 19 ]) which may result in a high probability of false positive results. In order to prevent this shortcoming, in this study, we analyzed four lncRNA-mRNA expression profile datasets (GSE106724, GSE114419, GSE137684, and GSE138518) using the MetaDE package and only selected the DELs and DEGs that overlapped in the four datasets.…”

“…Recently, with the development of the sequencing technique, there were some studies to mine the key lncRNAs [ 15 ], miRNAs [ 16 – 18 ], and mRNAs [ 15 , 17 , 19 ] in OGCs of PCOS patients using the gene or miRNA expression profile data. However, all of them focused only on the differentially expressed mRNAs (coding genes) (DEGs) [ 15 , 19 ], lncRNAs (DELs) [ 15 ], miRNAs (DEMs) alone [ 16 , 18 ], or DEM-DEG [ 17 ]. Also, the small molecule drugs that targeted them were not investigated.…”

Integrated Analysis of Hub Genes and miRNAs in Dilated Cardiomyopathy

“…GO enrichment analysis was also applied to develop the interaction network analysis between miRNAs, gene/mRNA, and transcription factors (already integrated the explored information of miRNA and potentially targeted gene/mRNAs) [ 17 – 19 ]. The enriched targets of DEMis and involved pathways were explored by previous methods [ 20 ].…”

Silencing Circ_0058063 Enhances Proliferation and Inhibits Apoptosis in PCOS Ovarian Granulosa Cells

“…Polycystic ovary syndrome (PCOS) is the most common endocrine disease in reproductive-aged women [1,2], affecting approximately 10% of women of childbearing age [3]. The most prominent characteristics of PCOS are abnormal follicular development and hyperandrogenism [4,5].…”