Identification of key pathways and genes in polycystic ovary syndrome via integrated bioinformatics analysis and prediction of small therapeutic molecules

Autor: Anandkumar Revanasiddapa Tengli, Basavaraj Vastrad, Chanabasayya Vastrad, Lata Telang, Iranna Kotturshetti, Praveenkumar Devarbhavi
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Adult
0301 basic medicine
lcsh:QH471-489
Drug Evaluation
Preclinical
Plasma membrane bounded cell projection
Computational biology
Biology
lcsh:Gynecology and obstetrics
03 medical and health sciences
0302 clinical medicine
Endocrinology
microRNA
Humans
lcsh:Reproduction
Gene Regulatory Networks
Protein Interaction Maps
Gene
Genetic Association Studies
Organelle envelope
lcsh:RG1-991
Gene Expression Profiling
Research
Neuron projection
Computational Biology
High-Throughput Nucleotide Sequencing
Obstetrics and Gynecology
biomarkers
expression profiling by high throughput sequencing
Polycystic ovary
pathway enrichment analysis
differentially expressed gene
Peptide metabolic process
Molecular Docking Simulation
Gene expression profiling
030104 developmental biology
Reproductive Medicine
polycystic ovary syndrome
Case-Control Studies
030220 oncology & carcinogenesis
Female
Developmental Biology
Zdroj: Reproductive Biology and Endocrinology, Vol 19, Iss 1, Pp 1-39 (2021)
Reproductive Biology and Endocrinology : RB&E
ISSN: 1477-7827
Popis: 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.
Databáze: OpenAIRE
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