Praveenkumar Devarbhavi
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Lata Telang
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Basavaraj Vastrad
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Anandkumar Revanasiddapa Tengli
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Chanabasayya Mallikarjunayya Vastrad
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Abstract
To add a enhance understanding of polycystic ovary syndrome (PCOS) at the molecular level, this investigation aimed to find the genes and crucial pathways linked with PCOS by using integrated bioinformatics analysis. Based on the expression profiling by high throughput sequencing data GSE84958 derived from the Gene Expression Omnibus, the differentially expressed genes (DEGs) between PCOS samples and normal controls were identified. With DEGs, we performed a series of functional enrichment analyses. Then, a protein–protein interaction (PPI) network, miRNA - target genes and TF - target gene networks were constructed and visualized, with which the hub gene nodes were screened out. Finally, validation of hub genes was performed by using receiver operating characteristic (ROC) and RT-PCR. Molecular docking studies performed. A total of 739 DEGs were screened out, among which 360 genes were up regulated and 379 genes were down regulated. GO enrichment analysis indicated that up regulated genes were mainly involved in peptide metabolic process, organelle envelope and RNA binding and the down regulated genes were significantly enriched in plasma membrane bounded cell projection organization, neuron projection and DNA-binding transcription factor activity, RNA polymerase II-specific. REACTOME pathway enrichment analysis showed that the up regulated genes were mainly enriched in translation and respiratory electron transport and the down regulated genes were mainly enriched in generic transcription pathway and transmembrane transport of small molecules. The top 10 hub genes in the constructed PPI network, miRNA - target gene network and TF - target gene network were SAA1, ADCY6, POLR2K, RPS15, RPS15A, CTNND1, ESR1, NEDD4L, KNTC1 and NGFR. The modules analysis showed that genes in the top 2 significant modules of PPI network were mainly associated with respiratory electron transport and signalling by NGF, respectively. We find a series of crucial genes along with the pathways that were most closely related with PCOS initiation and advancement. Our investigations provide a more detailed molecular mechanism for the progression of PCOS, detail information on the potential biomarkers and therapeutic targets.