Integrated Genomic and Bioinformatics Approaches to Identify Molecular Links between Endocrine Disruptors and Adverse Outcomes

Verga, Jacopo Umberto; Huff, Matthew; Owens, Diarmuid; Wolf, Bethany J.; Hardiman, Gary

doi:10.3390/ijerph19010574

Cited by 5 publications

(4 citation statements)

References 188 publications

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“…Koike et al showed that in mice exposed to DES, constant expression of the lactoferrin and EGF genes can be observed in the vagina and uterus [ 63 ]. Furthermore, Wang et al hypothesized that EGF could stimulate endometriosis cell proliferation by activating the Ras/Raf/MEK/ERK pathway [ 72 , 73 , 74 ].…”

Section: Environmental Impactmentioning

confidence: 99%

Endometriosis: Update of Pathophysiology, (Epi) Genetic and Environmental Involvement

2023

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Endometriosis is a chronic disease caused by ectopic endometrial tissue. Endometriotic implants induce inflammation, leading to chronic pain and impaired fertility. Characterized by their dependence on estradiol (via estrogen receptor β (ESRβ)) and their resistance to progesterone, endometriotic implants produce their own source of estradiol through active aromatase. Steroidogenic factor-1 (SF1) is a key transcription factor that promotes aromatase synthesis. The expression of SF1 and ESRβ is enhanced by the demethylation of their promoter in progenitor cells of the female reproductive system. High local concentrations of estrogen are involved in the chronic inflammatory environment favoring the implantation and development of endometriotic implants. Similar local conditions can promote, directly and indirectly, the appearance and development of genital cancer. Recently, certain components of the microbiota have been identified as potentially promoting a high level of estrogen in the blood. Many environmental factors are also suspected of increasing the estrogen concentration, especially prenatal exposure to estrogen-like endocrine disruptors such as DES and bisphenol A. Phthalates are also suspected of promoting endometriosis but throughmeans other than binding to estradiol receptors. The impact of dioxin or tobacco seems to be more controversial.

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Section: Environmental Impactmentioning

confidence: 99%

Endometriosis: Update of Pathophysiology, (Epi) Genetic and Environmental Involvement

2023

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“…The complex methods by which EEDs affect the genes involved in vascular remodeling and contribute to the onset of PAD are uncovered in this study using gene network analysis. This method makes it easier to identify important genes, their regulatory connections, and probable pathways that EEDs may disrupt, providing insights into the molecular causes of vascular disorders [13,14].…”

Section: Introductionmentioning

confidence: 99%

“…The resulting gene network analysis is built on this integrated dataset, which offers a thorough understanding of the molecular dynamics relating to EEDs and vascular remodeling in PAD. Combining bioinformatics methods with various data sources enables a more comprehensive comprehension of the intricate biological mechanisms behind vascular disorders and environmental influences [14,15].…”

Section: Introductionmentioning

confidence: 99%

Integrative Bioinformatics–Gene Network Approach Reveals Linkage between Estrogenic Endocrine Disruptors and Vascular Remodeling in Peripheral Arterial Disease

Avecilla,

Doke,

Das

et al. 2024

IJMS

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Vascular diseases, including peripheral arterial disease (PAD), pulmonary arterial hypertension, and atherosclerosis, significantly impact global health due to their intricate relationship with vascular remodeling. This process, characterized by structural alterations in resistance vessels, is a hallmark of heightened vascular resistance seen in these disorders. The influence of environmental estrogenic endocrine disruptors (EEDs) on the vasculature suggests a potential exacerbation of these alterations. Our study employs an integrative approach, combining data mining with bioinformatics, to unravel the interactions between EEDs and vascular remodeling genes in the context of PAD. We explore the molecular dynamics by which EED exposure may alter vascular function in PAD patients. The investigation highlights the profound effect of EEDs on pivotal genes such as ID3, LY6E, FOS, PTP4A1, NAMPT, GADD45A, PDGF-BB, and NFKB, all of which play significant roles in PAD pathophysiology. The insights gained from our study enhance the understanding of genomic alterations induced by EEDs in vascular remodeling processes. Such knowledge is invaluable for developing strategies to prevent and manage vascular diseases, potentially mitigating the impact of harmful environmental pollutants like EEDs on conditions such as PAD.

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“…With the advancement of genomic technology, bioinformatics has grown in popularity for analyzing gene expression patterns in order to better understand the molecular processes behind illnesses and to identify meaningful therapeutic targets ( Cantelli et al, 2022 ; Verga et al, 2022 ). Weighted Gene Co-expression Network Analysis (WGCNA) is a critical technique for deciphering gene function and association from genome-wide expression ( Liang et al, 2022 ; Rezaei et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Upregulated ENC1 predicts unfavorable prognosis and correlates with immune infiltration in endometrial cancer

He²,

Luo

et al. 2022

Front. Cell Dev. Biol.

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A better knowledge of the molecular process behind uterine corpus endometrial carcinoma (UCEC) is important for prognosis prediction and the development of innovative targeted gene therapies. The purpose of this research is to discover critical genes associated with UCEC. We analyzed the gene expression profiles of TCGA-UCEC and GSE17025, respectively, using Weighted Gene Co-expression Network Analysis (WGCNA) and differential gene expression analysis. From four sets of findings, a total of 95 overlapping genes were retrieved. On the 95 overlapping genes, KEGG pathway and GO enrichment analysis were conducted. Then, we mapped the PPI network of 95 overlapping genes using the STRING database. Twenty hub genes were evaluated using the Cytohubba plugin, including NR3C1, ATF3, KLF15, THRA, NR4A1, FOSB, PER3, HLF, NTRK3, EGR3, MAPK13, ARNTL2, PKM2, SCD, EIF5A, ADHFE1, RERGL, TUB, and ENC1. The expression levels of NR3C1, PKM2, and ENC1 were shown to be adversely linked with the survival time of UCEC patients using univariate Cox regression analysis and Kaplan-Meier survival calculation. ENC1 were also overexpressed in UCEC tumor tissues or cell lines, as shown by quantitative real-time PCR and Western blotting. Then we looked into it further and discovered that ENC1 expression was linked to tumor microenvironment and predicted various immunological checkpoints. In conclusion, our data indicate that ENC1 may be required for the development of UCEC and may serve as a future biomarker for diagnosis and therapy.

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Integrated Genomic and Bioinformatics Approaches to Identify Molecular Links between Endocrine Disruptors and Adverse Outcomes

Cited by 5 publications

References 188 publications

Endometriosis: Update of Pathophysiology, (Epi) Genetic and Environmental Involvement

Endometriosis: Update of Pathophysiology, (Epi) Genetic and Environmental Involvement

Integrative Bioinformatics–Gene Network Approach Reveals Linkage between Estrogenic Endocrine Disruptors and Vascular Remodeling in Peripheral Arterial Disease

Upregulated ENC1 predicts unfavorable prognosis and correlates with immune infiltration in endometrial cancer

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