Epigenomes

13 pages, 510 KB

Open AccessArticle

Differences in MicroRNA Expression in Firefighters Responding to a Train Derailment and Fire in East Palestine, Ohio

by Jaclyn M. Goodrich, Yaodong Xin, Shawn C. Beitel, John Gulotta, Lu Wang, Bhavya Thotakura, Judith M. Graber, Derek Urwin, Alexander C. Mayer, Sara Jahnke, Derrick L. Edwards, Casey Grant, Sreenivasan Ranganathan and Jefferey L. Burgess

Epigenomes 2026, 10(1), 8; https://doi.org/10.3390/epigenomes10010008 - 3 Feb 2026

Abstract

Background/Objectives: High-risk, low-frequency incidents such as building collapses and large chemical fires can result in acute, high-dose exposures to toxic agents for first responders and the surrounding community. While these exposures may last for hours to days, their contribution to firefighters’ risks [...] Read more.

Background/Objectives: High-risk, low-frequency incidents such as building collapses and large chemical fires can result in acute, high-dose exposures to toxic agents for first responders and the surrounding community. While these exposures may last for hours to days, their contribution to firefighters’ risks for cancer and other diseases is relatively unknown. In February 2023, a freight train transporting chemicals derailed and caught fire in East Palestine, Ohio, US. More than 350 firefighters, primarily volunteer, responded to the incident. In this cross-sectional study, we evaluated epigenetic markers of toxicity in responding firefighters. We hypothesized that exposures from responding to the train derailment would alter the expression of microRNAs (miRNAs) linked to carcinogenesis. Methods: We enrolled 62 responding firefighters and a comparison group of 26 firefighters from the same region who did not respond to the incident. We measured the relative expression of 800 miRNAs in blood samples using the nCounter Human v3 miRNA expression panel. We compared the expression of miRNA between exposure groups in negative binomial regression models, adjusting for potential confounders. Results: At a false discover rate cut-off of 5% (q-value < 0.05), 16 miRNAs had significantly higher expression and one significantly lower among firefighters that responded to the incident. Top disease-related pathways in which these miRNAs were enriched included those relevant to neurodegenerative diseases, vascular disease, and multiple cancer sites. Conclusions: Overall, results suggest responding to one large incident can have non-transient impacts on miRNA expression. Whether this translates into longer-term health risks or adaptive responses to exposures is unclear. Full article

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12 pages, 4978 KB

Open AccessArticle

An Hsp70 Chaperone Is Involved in Meiotic Silencing by Unpaired DNA

by Victor T. Sy, Sterling S. Trawick, Hagen M. Tatarsky and Patrick K. T. Shiu

Epigenomes 2026, 10(1), 7; https://doi.org/10.3390/epigenomes10010007 - 26 Jan 2026

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Abstract

In the filamentous fungus Neurospora crassa, a gene not having a pairing partner during meiosis is seen as a potential intruder and is targeted by a mechanism called meiotic silencing by unpaired DNA (MSUD). MSUD employs core RNA interference (RNAi) components such [...] Read more.

In the filamentous fungus Neurospora crassa, a gene not having a pairing partner during meiosis is seen as a potential intruder and is targeted by a mechanism called meiotic silencing by unpaired DNA (MSUD). MSUD employs core RNA interference (RNAi) components such as the SMS-2 Argonaute, which uses small interfering RNAs (siRNAs) as guides to seek out mRNAs from unpaired genes for silencing. In Drosophila melanogaster, the heat shock protein 70 (Hsp70) chaperone system facilitates the conformational activation of an Argonaute and allows it to load siRNAs. Here, our results demonstrate that an Hsp70 protein in Neurospora interacts with SMS-2 and mediates the silencing of unpaired genes. Full article

(This article belongs to the Collection Feature Papers in Epigenomes)

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11 pages, 1968 KB

Open AccessArticle

ARS2, a Cofactor of CBC, Promotes Meiotic Silencing by Unpaired DNA

by Michael M. Vierling, Victor T. Sy, Logan M. Decker, Hua Xiao, Justine N. Hemaya and Patrick K. T. Shiu

Epigenomes 2026, 10(1), 6; https://doi.org/10.3390/epigenomes10010006 - 21 Jan 2026

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Abstract

The presence of an extra DNA segment in a genome could indicate a transposon or another repetitive element on the move. In Neurospora crassa, a surveillance mechanism called meiotic silencing by unpaired DNA (MSUD) is maintained to monitor these selfish elements. MSUD [...] Read more.

The presence of an extra DNA segment in a genome could indicate a transposon or another repetitive element on the move. In Neurospora crassa, a surveillance mechanism called meiotic silencing by unpaired DNA (MSUD) is maintained to monitor these selfish elements. MSUD utilizes common RNA interference (RNAi) factors, including the SMS-2 Argonaute, to target mRNAs from genes lacking a pairing partner during meiosis. In eukaryotes, an mRNA transcript is typically bound at the 5′ cap by the cap-binding complex (CBC), which assists in its nuclear export. Previously, we discovered that CBC and its interactor NCBP3 mediate MSUD, possibly by guiding the perinuclear SMS-2 to effectively recognize exported mRNAs. Here, we report that ARS2, a CBC cofactor, is involved in MSUD. ARS2 interacts with both CBC and NCBP3, and it may help bring them together. In addition to its role in silencing, ARS2 also contributes to vegetative growth and sexual sporulation. Full article

(This article belongs to the Collection Feature Papers in Epigenomes)

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18 pages, 2156 KB

Open AccessReview

Something Old, Something New, Something Borrowed… About the Placenta

by Nadezhda Milova, Maria Nikolova, Angel Yordanov, Antoan Milov and Stoilka Mandadzhieva

Epigenomes 2026, 10(1), 5; https://doi.org/10.3390/epigenomes10010005 - 19 Jan 2026

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Abstract

The connection between the mother and the child has been considered one of the strongest bonds in nature. Though there are numerous factors that can influence the establishment of pregnancy, in its essence, three are considered major: a good quality embryo, a receptive [...] Read more.

The connection between the mother and the child has been considered one of the strongest bonds in nature. Though there are numerous factors that can influence the establishment of pregnancy, in its essence, three are considered major: a good quality embryo, a receptive endometrium, and successful cross-talk between them. The placenta, which derives from the trophoblast of the embryo, develops when a successful implantation occurs. It is an ephemeral organ through which the turnover of nutrients, gases, and waste molecules is realized. It serves as a barrier and can provide the embryo with immune factors. Placental disorders are observed in some rare but life-threatening obstetric conditions like preeclampsia (PE), fetal growth restriction (FGR), gestational trophoblastic diseases (GTDs), and gestational diabetes mellitus (GDM). The etiology and pathogenesis of some are still partially enigmatic. Our attention in this review was driven by the participation of small RNA molecules—miRNAs and piRNAs—as potential epigenetic modulators of genes that play a pivotal role in placental functioning. In this study, we analyze the influence of these epigenetic factors on the mechanisms of the development of preeclampsia. The molecular approach for understanding placental disorders may help new diagnostic and therapeutic solutions to be found. Full article

(This article belongs to the Collection Feature Papers in Epigenomes)

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12 pages, 257 KB

Open AccessReview

Epigenetic Alterations in Colitis-Associated Colorectal Cancer

by Nisha Ganesh, William M. Grady and Andrew M. Kaz

Epigenomes 2026, 10(1), 4; https://doi.org/10.3390/epigenomes10010004 - 16 Jan 2026

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Abstract

Colitis-associated colorectal cancer (CAC) represents a distinct subtype of colorectal malignancy that arises in the setting of chronic inflammatory bowel disease (IBD). Unlike sporadic colorectal cancer, CAC develops through inflammation-driven molecular pathways, in which epigenetic alterations play a pivotal role in tumor initiation [...] Read more.

Colitis-associated colorectal cancer (CAC) represents a distinct subtype of colorectal malignancy that arises in the setting of chronic inflammatory bowel disease (IBD). Unlike sporadic colorectal cancer, CAC develops through inflammation-driven molecular pathways, in which epigenetic alterations play a pivotal role in tumor initiation and progression. This review highlights the major epigenetic mechanisms implicated in CAC, including DNA methylation, histone modifications, and microRNA (miRNA) dysregulation. Aberrant DNA methylation patterns, such as promoter hypermethylation of tumor suppressor genes and global hypomethylation, contribute to genomic instability and altered gene expression. In parallel, inflammation-induced changes in histone configuration modulate chromatin accessibility and transcriptional activity of key oncogenic and tumor-suppressive pathways. Furthermore, deregulated miRNAs influence multiple aspects of CAC pathogenesis by targeting genes involved in inflammation and tumor progression. Understanding these epigenetic processes provides valuable insights into the development of colorectal malignancy and identifies potential biomarkers for early detection and intervention in colitis-associated colorectal cancer. Full article

(This article belongs to the Special Issue Epigenetic Signatures in Metabolic Health and Cancer)

17 pages, 2282 KB

Open AccessArticle

Fisetin Suppresses the Proliferative and Migratory Behavior of HeLa Cells by Modulating Aberrant Epigenetic Marks (Writers and Erasers)

by Nazia Afroze, Reham I. Alagal, Lujain A. Almousa, Ritu Raina, Prathap Bava, Lizna Mohamed Ali, Tarique Noorul Hasan and Arif Hussain

Epigenomes 2026, 10(1), 3; https://doi.org/10.3390/epigenomes10010003 - 12 Jan 2026

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Abstract

Purpose: The reversible deviant in epigenomic modulations is the highlight of developing new anti-cancer drugs, necessitating the use of fisetin as an epigenetic modifier in the study. Methods: In silico and molecular studies were performed to analyze the modulatory effect of fisetin on [...] Read more.

Purpose: The reversible deviant in epigenomic modulations is the highlight of developing new anti-cancer drugs, necessitating the use of fisetin as an epigenetic modifier in the study. Methods: In silico and molecular studies were performed to analyze the modulatory effect of fisetin on various writers and erasers. Further, whole genome DNA methylation sequencing and expression studies were performed. Global DNA methylation-LINE 1 kit was used to check global DNA methylation. Additionally, the effect of fisetin on migration was evaluated by colony, scratch, and invasion assays and qPCR and protein expression studies of migration-related genes were carried out on HeLa cells. Results: In silico studies have supported that fisetin interacts with writers and erasers in their catalytic site and the simulation studies showed minimum fluctuations in energy and temperature over a 10 ns timescale indicating that these complexes are likely to remain stable. Fisetin (20–50 µM) dose-dependently inhibited DNA methyltransferases (DNMT), histone deacetyl transferases (HDAC), histone acetyl transferases (HAT), and histone methyltransferases (HMT) activities at 48 h, with inhibition ranging from 24 to 72% compared to the control. The expression and enzymatic activity of these proteins, along with various H4 and H3 modification marks, were observed to be altered following fisetin treatment at 48 h. Fisetin treatment reduced promoter methylation in various tumor suppressor genes ranging from 15.29% to 76.23% and leading to the corresponding reactivation of important tumor suppressor genes; however, it did not lead to any alteration in the global DNA methylation compared to untreated controls linked with the anti-migratory properties of fisetin as the percentage of migrated cells dropped from ~40% to ~8%. Conclusions: This study gives a mechanistic insight of fisetin as a potential epigenetic modifier in HeLa cells. Full article

(This article belongs to the Collection Epigenetic Regulation of Cellular Differentiation)

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16 pages, 1732 KB

Open AccessArticle

Epigenetic Regulation and Gene Expression Profiles in Cervical Swabs: Toward Non-Invasive Biomarkers of Cervical Lesion Progression

by Ivana Kašubová, Andrea Hornáková, Lucia Kotúľová, Tomáš Rokos, Zuzana Kolková, Andrea Kapinová, Terézia Pribulová, Erik Kozubík, Michal Kalman, Kamil Biringer, Erik Kúdela and Veronika Holubeková

Epigenomes 2026, 10(1), 2; https://doi.org/10.3390/epigenomes10010002 - 7 Jan 2026

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Abstract

Background/Objectives: Cervical cancer is a common malignancy in women worldwide, closely associated with persistent human papillomavirus (HPV) infection. Epigenetic mechanisms, particularly promoter methylation, may contribute to tumour progression. This pilot study aimed to analyse the promoter methylation patterns and gene expression of [...] Read more.

Background/Objectives: Cervical cancer is a common malignancy in women worldwide, closely associated with persistent human papillomavirus (HPV) infection. Epigenetic mechanisms, particularly promoter methylation, may contribute to tumour progression. This pilot study aimed to analyse the promoter methylation patterns and gene expression of selected genes (DNMT, BCL2, CDH1, CD8A, MUC1, ALCAM). The goal was to identify associations between promoter hypermethylation, gene expression, and HPV infection in cervical swab specimens obtained from patients with low-grade squamous intraepithelial lesions (SILs), high-grade SILs, or squamous cell carcinomas. Methods: A total of 81 cervical swab samples from Slovak participants were included in the study. DNA methylation and gene expression profiling was performed using real-time PCR (qPCR) and pyrosequencing. Results: BCL2 expression was significantly reduced across all lesion grades. CD8A expression was slightly elevated in low- and high-grade SILs, particularly in HPV-positive samples. MUC1 showed variability with lesion grade. No statistically significant differences in DNA methylation were observed across groups stratified by HPV status, community state type, and lesion grade. Conclusions: Our findings suggest that BCL2 downregulation and gene activity variability influenced by the vaginal microbiome may play a role in cervical lesion progression. These results highlight potential non-invasive biomarkers for monitoring cervical lesions. Full article

(This article belongs to the Special Issue Epigenetic Signatures in Metabolic Health and Cancer)

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19 pages, 1291 KB

Open AccessArticle

Upregulation of a MicroRNA Signature Involving miR-17-5p, miR-26b-5p, miR-106a-5p, and miR-146a-5p During Cervical Epithelial Transformation

by Andrea Hornakova, Zuzana Kolkova, Lucia Kotulova, Tomas Rokos, Ivana Kasubova, Terezia Pribulova, Erik Kozubik, Kamil Biringer, Erik Kudela and Veronika Holubekova

Epigenomes 2026, 10(1), 1; https://doi.org/10.3390/epigenomes10010001 - 26 Dec 2025

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Abstract

Background: Cervical cancer remains the fourth most common malignancy among women worldwide. Despite vaccination and regular screening, new molecular biomarkers are needed for improved early detection and risk assessment. MicroRNAs (miRNAs) play crucial roles in post-transcriptional regulation, and their dysregulation may contribute [...] Read more.

Background: Cervical cancer remains the fourth most common malignancy among women worldwide. Despite vaccination and regular screening, new molecular biomarkers are needed for improved early detection and risk assessment. MicroRNAs (miRNAs) play crucial roles in post-transcriptional regulation, and their dysregulation may contribute to cervical carcinogenesis. This study evaluated the expression of selected miRNAs in cervical swab samples and corresponding biopsies from women with various grades of cervical lesions and assessed their relationship with human papillomavirus (HPV) infection. Methods: A total of 72 cervical swab samples were included in this study, divided according to cytological severity: negative for intraepithelial lesion or malignancy (NILM, n = 15), atypical squamous cells of undetermined significance (ASC-US, n = 12), low-grade squamous intraepithelial lesion (LSIL, n = 19), and high-grade squamous intraepithelial lesion (HSIL, n = 26). In a subset of patients, corresponding biopsy specimens were analysed for comparison. The association of miRNA expression with HPV infection status was also examined. miRNA expression was quantified by real-time PCR using commercially available assays. Results: To assess the relationship between miRNA expression, lesion severity, and HPV infection, fold change values were compared to the control group (NILM). No significant differences were observed in the ASC-US group (p > 0.05). In contrast, several miRNAs were significantly upregulated in the LSIL and/or HSIL groups, as well as in HPV-positive samples, indicating their association with both lesion progression and viral infection. Specifically, miR-17-5p, miR-26b-5p, miR-29a-3p, miR-103a-3p, miR-106a-5p, miR-146a-5p, miR-155-5p, and miR-191-5p showed increased expression (p < 0.05) compared with controls. The observed upregulation of miR-26b-5p, miR-106a-5p, and miR-146a-5p highlights their potential role in HPV-associated cervical carcinogenesis. Dysregulated miRNAs were enriched in pathways related to infectious diseases, various types of cancer, and cell adhesion processes. Conclusions: The gradual increase in specific miRNAs with lesion severity and HPV infection suggests their role in cervical carcinogenesis. The identified miRNAs may serve as promising non-invasive biomarkers for early detection and monitoring of HPV-associated cervical lesions. Full article

(This article belongs to the Special Issue Epigenetic Signatures in Metabolic Health and Cancer)

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Epigenomes, Volume 10, Issue 1 (March 2026) – 8 articles

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