Transcriptomic screening to identify hub genes and drug signatures for PCOS based on RNA-Seq data in granulosa cells

Zanjirband, M.; Baharlooie, Maryam; Safaeinejad, Z.; Nasr-Esfahani, Mohammad Hossein

doi:10.1016/j.compbiomed.2023.106601

Cited by 6 publications

(3 citation statements)

References 73 publications

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“…In PCOS, altered GC functions contribute to abnormal folliculogenesis, including decreased apoptosis, defective proliferation, abnormal hypersensitivity to FSH stimulation, and altered steroidogenesis [ 28 , 145 – 147 ]. A multi-omics investigation further confirmed that DEGs involved in steroid production and metabolic signaling cluster differently in PCOS-derived GCs than in normal GCs [ 148 – 150 ]. Indeed, an altered oocyte microenvironment with perturbed gene expression in both human and murine PCOS-derived GCs has been demonstrated [ 151 , 152 ].…”

Section: Progression Of Induced Pluripotent Stem Cell (Ipsc) Technolo...mentioning

confidence: 96%

Induced Pluripotent Stem Cells as a Possible Approach for Exploring the Pathophysiology of Polycystic Ovary Syndrome (PCOS)

Khatun,

Lundin,

Naillat

et al. 2023

Stem Cell Rev and Rep

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Polycystic ovary syndrome (PCOS) is the most prevalent endocrine condition among women with pleiotropic sequelae possessing reproductive, metabolic, and psychological characteristics. Although the exact origin of PCOS is elusive, it is known to be a complex multigenic disorder with a genetic, epigenetic, and environmental background. However, the pathogenesis of PCOS, and the role of genetic variants in increasing the risk of the condition, are still unknown due to the lack of an appropriate study model. Since the debut of induced pluripotent stem cell (iPSC) technology, the ability of reprogrammed somatic cells to self-renew and their potential for multidirectional differentiation have made them excellent tools to study different disease mechanisms. Recently, researchers have succeeded in establishing human in vitro PCOS disease models utilizing iPSC lines from heterogeneous PCOS patient groups (iPSCPCOS). The current review sets out to summarize, for the first time, our current knowledge of the implications and challenges of iPSC technology in comprehending PCOS pathogenesis and tissue-specific disease mechanisms. Additionally, we suggest that the analysis of polygenic risk prediction based on genome-wide association studies (GWAS) could, theoretically, be utilized when creating iPSC lines as an additional research tool to identify women who are genetically susceptible to PCOS. Taken together, iPSCPCOS may provide a new paradigm for the exploration of PCOS tissue-specific disease mechanisms.

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Section: Progression Of Induced Pluripotent Stem Cell (Ipsc) Technolo...mentioning

confidence: 96%

Induced Pluripotent Stem Cells as a Possible Approach for Exploring the Pathophysiology of Polycystic Ovary Syndrome (PCOS)

Khatun,

Lundin,

Naillat

et al. 2023

Stem Cell Rev and Rep

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show abstract

“…Genomics, transcriptomics, proteomics and metabolomics studies have been performing with the aim of identifying the molecular pathways involved in the pathogenesis of PCOS. By way of example, RNA-sequencing (RNA-Seq) and microarray-based comparison of ovarian tissue from PCOS women with the controls revealed that Wnt (Wingless-related integration site) signaling pathway, insulin receptor signaling pathway, MAPK (Mitogen-Activated Protein Kinase) signaling pathway, aberrant status of mitochondrial energy metabolism, TNF (Tumor Necrosis Factor) signaling pathway, regulation of cell cycle and apoptosis are likely to be involved in the PCOS development 2 – 5 . However, according to our knowledge, the role of p53 pathway has never been investigated in this disease.…”

Section: Introductionmentioning

confidence: 99%

“…pathway, regulation of cell cycle and apoptosis are likely to be involved in the PCOS development [2][3][4][5] . However, according to our knowledge, the role of p53 pathway has never been investigated in this disease.…”

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confidence: 99%

Evaluation of the p53 pathway in polycystic ovarian syndrome pathogenesis and apoptosis enhancement in human granulosa cells through transcriptome data analysis

Zanjirband,

Hodayi,

Safaeinejad

et al. 2023

Sci Rep

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The polycystic ovarian syndrome (PCOS) is closely associated with enhanced apoptosis of granulosa cells, which have a vital role in maturation of oocytes. p53 plays a critical role in the regulation of apoptosis and cell cycle arrest, metabolism and insulin resistance. The aim of this study was to investigate the impact of p53 pathway in enhancing apoptosis and abnormal function of granulosa cells. In this study, microarray analysis and RNA sequencing were downloaded from the GEO and used as datasets. Principal Component Analysis (PCA) and online SSizer tool were applied to evaluate the experiment quality control and sample sufficiency, respectively. Bioinformatics’ analyses were performed on the selected datasets, and validated by qRT-PCR and western blot analyses. Three datasets out of five ones were chosen for re-analyzing based on the PCA outcomes. 21 deregulated genes were identified via filters including p < 0.05 and |log2FC|≥ 1. Functional enrichment analysis confirmed the relevance of cell cycle regulation and apoptosis as common biological hallmarks in PCOS. Results have shown differentially expressed p53 target genes involved in apoptosis (BAX, FAS, PMAIP1, and CASP8), cell cycle (Cyclins, Cyclin dependent kinases), glucose metabolism and insulin resistance (THBS1), and p53 regulation (MDM2). Subsequently, the relative mRNA expression of FAS, PMAIP1 and MDM2 genes, and protein levels of p53 and MDM2 were confirmed using granulosa cells collected from 20 PCOS women and 18 control individuals by qRT-PCR and western blot, respectively. Results of this study represent the possible role of p53 pathway in pathogenesis of PCOS particularly, through the enhancement of apoptosis in granulosa cells.

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Sine cosine algorithm-based feature selection for improved machine learning models in polycystic ovary syndrome diagnosis

Rajput,

Tyagi,

Gupta

et al. 2024

Multimed Tools Appl

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Transcriptomic screening to identify hub genes and drug signatures for PCOS based on RNA-Seq data in granulosa cells

Cited by 6 publications

References 73 publications

Induced Pluripotent Stem Cells as a Possible Approach for Exploring the Pathophysiology of Polycystic Ovary Syndrome (PCOS)

Induced Pluripotent Stem Cells as a Possible Approach for Exploring the Pathophysiology of Polycystic Ovary Syndrome (PCOS)

Evaluation of the p53 pathway in polycystic ovarian syndrome pathogenesis and apoptosis enhancement in human granulosa cells through transcriptome data analysis

Sine cosine algorithm-based feature selection for improved machine learning models in polycystic ovary syndrome diagnosis

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