Nicotine attenuates global genomic DNA methylation by influencing DNMTs gene expression in human endometrial stromal cells

Zal, Fatemeh; Yarahmadi, Amir; Totonchi, Hamidreza; Barazesh, Mahdi; Sarabi, Mostafa Moradi

doi:10.1186/s41021-020-0144-5

Cited by 7 publications

(5 citation statements)

References 53 publications

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“…Sahin et al indicated that smoking has decreased the expression of CXCL-12 and FGF2 [6]; our study con rmed their results and showed that nicotine exposure can decrease the expression of CXCL-12 and FGF2 genes. Furthermore, another study demonstrated that treatment of endometrial stromal cells with nicotine at concentrations of 10 − 11 µM, 10 − 8 µM, and 10 − 6 µM for 24 h results in decreased expression of DNA methyl-transferases (DNMTs) and decreases global genomic DNA methylation levels, which con rms our results [64].…”

Section: Resultssupporting

confidence: 88%

Adverse effects of nicotine on endometrium receptivity markers: and protective effect of caffeic acid phenyl ester

Namdari

MOHAMMADIAN

Khajeh

et al. 2020

Preprint

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Background nicotine adversely affects the female reproductive system and changes the methylation pattern of some genes in the placenta. In contrast, caffeic acid phenylethyl ester) CAPE (, as a potent antioxidant, has protective effects against the harmful effects of oxygen free radical molecules, methotrexate, and pesticides on the reproductive system. To find the effect of nicotine on the endometrium, we investigated three markers of endometrium receptivity including fibroblast growth factor 2, vascular endothelial growth factors A, and C-X-C motif chemokine ligand 12 and also changes in methylation levels of CXCL-12 gene promoter. In addition, we evaluated the protective effect of CAPE against nicotine. Methods the appropriate treatment dose was selected based on the literature, the endometrial stromal cells were divided into 4 groups, including control, treated with nicotine, CAPE, and nicotine followed by CAPE. Finally, the quantitative polymerase chain reaction and Methylation-Specific PCR were carried out. Results The results showed that treatment of endometrial stromal cells with nicotine (10− 6 µM) for 24 h significantly reduced expression of CXCL-12, FGF, and VEGFA genes. However, a decrease in CXCL-12 expression was not associated with increased methylation levels in the studied promoter region. In contrast, endometrial stromal cells treated with CAPE (4 µg/ml) for 24 h adverse significantly nicotine-induced reduction of CXCL-12, FGF, and VEGFA genes expression. Conclusion Exposure to nicotine has negative effects on uterine receptivity, implantation, and fertility, via reducing the expression of VEGFA, CXCL-12, and FGF2 genes. In contrast, CAPE has a protective effects and improves these genes expression.

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Section: Resultssupporting

confidence: 88%

Adverse effects of nicotine on endometrium receptivity markers: and protective effect of caffeic acid phenyl ester

Namdari

MOHAMMADIAN

Khajeh

et al. 2020

Preprint

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“… 40 – 42 Nicotine could attenuate DNA methylation by regulating the expression of DNMTs in human endometrial stromal cells. 43 However, previous studies commonly explored solo types of epigenetic modifications. In our study, we systematically investigated the smoking-related DNA methylation, lncRNA, and miRNA in bladder cancer, and identified 1078 DNA methylations, 506 lncRNAs, and 102 miRNAs.…”

Section: Discussionmentioning

confidence: 99%

Smoking-related epigenetic modifications are associated with the prognosis and chemotherapeutics of patients with bladder cancer

Ling

Zhou

2023

Int J Immunopathol Pharmacol

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Objective Epidemiologic studies have linked smoking to various malignancies, including bladder cancer, but its underlying biological functions remain elusive. Currently, we aimed to identify the smoking-related epigenetic modifications and disclose their impacts on prognosis and therapies in bladder cancer. Methods DNA methylation, transcriptome, and clinical profiles were acquired from The Cancer Genome Atlas (TCGA) using “TCGAbiolinks” Differential expression analyses were performed with “limma” and visualized by the “pheatmap” package. Smoking-related interactions were displayed using Cytoscape. Least absolute shrinkage and selection operator (LASSO) algorithm was for generation of a smoking-related prognostic model. Kaplan–Meier analysis with log-rank test was for survival analysis, followed by a prognostic nomogram. The Gene Set Enrichment Analysis (GSEA) was used for functional analysis. The “oncoPredict” package was applied for drug sensitivity analysis. Results We recruited all types of bladder cancers and found that smoking was involved in poor prognosis, with the hazard ratio (HR) of 1.600 (95%CI: 1.028–2.491). A total of 1078 smoking-related DNA methylations (526 hypermethylation and 552 hypomethylation) were identified and 9 methylation-driven genes differentially expressed in bladder cancer. Also, 506lncRNAs (448 upregulated and 58 downregulated lncRNAs) and 102 miRNAs (74 upregulated and 28 downregulated miRNAs) were determined as smoking-related ncRNAs. We then calculated the smoking-related risk score and observed that cases of high risk were predicted with poor prognosis. We constructed a prognostic nomogram to predict the 1-, 3-, and 5-year overall survival rates. Several cancer-related pathways were enriched in the high-risk group, and patients with high-risk were more sensitive to Gemcitabine, Wnt-C59, JAK1_8709, KRAS (G12C) Inhibitor-12, and LY2109761. Whereas, those with low-risk were more sensitive to Cisplatin, AZ960, and Buparlisib. Conclusions Totally, we initially identified the smoking-related epigenetic modifications in bladder cancer and constructed a corresponding prognostic model, which was also linked to disparate sensitivities to chemotherapeutics. Our findings would provide novel insights into the carcinogenesis, prognosis, and therapies in bladder cancer.

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“…Tobacco smoking further modulates the epigenomic landscape at different levels. First, tobacco constituents such as nicotine may alter the levels of selected DNMTs, including the downregulation of DNMT3A and DNMT3B [88] and the upregulation of DNMT1 [89]. Second, carcinogens in cigarette smoke such as nitrosamines or formaldehyde can damage DNA by introducing double strand breaks, which is a main cause of mutations.…”

Section: Smoking and Other Environmental Factorsmentioning

confidence: 99%

Epigenetic Reprogramming of Tumor-Associated Fibroblasts in Lung Cancer: Therapeutic Opportunities

Alcaraz

Ikemori

Llorente

et al. 2021

Cancers

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Lung cancer is the leading cause of cancer-related death worldwide. The desmoplastic stroma of lung cancer and other solid tumors is rich in tumor-associated fibroblasts (TAFs) exhibiting an activated/myofibroblast-like phenotype. There is growing awareness that TAFs support key steps of tumor progression and are epigenetically reprogrammed compared to healthy fibroblasts. Although the mechanisms underlying such epigenetic reprogramming are incompletely understood, there is increasing evidence that they involve interactions with either cancer cells, pro-fibrotic cytokines such as TGF-β, the stiffening of the surrounding extracellular matrix, smoking cigarette particles and other environmental cues. These aberrant interactions elicit a global DNA hypomethylation and a selective transcriptional repression through hypermethylation of the TGF-β transcription factor SMAD3 in lung TAFs. Likewise, similar DNA methylation changes have been reported in TAFs from other cancer types, as well as histone core modifications and altered microRNA expression. In this review we summarize the evidence of the epigenetic reprogramming of TAFs, how this reprogramming contributes to the acquisition and maintenance of a tumor-promoting phenotype, and how it provides novel venues for therapeutic intervention, with a special focus on lung TAFs.

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Nicotine attenuates global genomic DNA methylation by influencing DNMTs gene expression in human endometrial stromal cells

Cited by 7 publications

References 53 publications

Adverse effects of nicotine on endometrium receptivity markers: and protective effect of caffeic acid phenyl ester

Adverse effects of nicotine on endometrium receptivity markers: and protective effect of caffeic acid phenyl ester

Smoking-related epigenetic modifications are associated with the prognosis and chemotherapeutics of patients with bladder cancer

Epigenetic Reprogramming of Tumor-Associated Fibroblasts in Lung Cancer: Therapeutic Opportunities

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