EpigenomicsPub Date : 2024-03-26DOI: 10.2217/epi-2023-0374
Irene Fischetti, Laura Botti, Roberta Sulsenti, Valeria Cancila, Claudia Enriquez, Renata Ferri, Marco Bregni, Filippo Crivelli, Claudio Tripodo, Mario P Colombo, Elena Jachetti
{"title":"Combined therapy targeting AR and EZH2 curbs castration-resistant prostate cancer enhancing anti-tumor T-cell response.","authors":"Irene Fischetti, Laura Botti, Roberta Sulsenti, Valeria Cancila, Claudia Enriquez, Renata Ferri, Marco Bregni, Filippo Crivelli, Claudio Tripodo, Mario P Colombo, Elena Jachetti","doi":"10.2217/epi-2023-0374","DOIUrl":"10.2217/epi-2023-0374","url":null,"abstract":"<p><p><b>Aim:</b> Castration-resistant prostate cancer (CRPC) eventually becomes resistant to androgen receptor pathway inhibitors like enzalutamide. Immunotherapy also fails in CRPC. We propose a new approach to simultaneously revert enzalutamide resistance and rewire anti-tumor immunity. <b>Methods:</b> We investigated <i>in vitro</i> and in subcutaneous and spontaneous mouse models the effects of combining enzalutamide and GSK-126, a drug inhibiting the epigenetic modulator EZH2. <b>Results:</b> Enzalutamide and GSK-126 synergized to reduce CRPC growth, also restraining tumor neuroendocrine differentiation. The anti-tumor activity was lost in immunodeficient mice. Indeed, the combination treatment awoke cytotoxic activity and IFN-γ production of tumor-specific CD8<sup>+</sup> T lymphocytes. <b>Conclusion:</b> These results promote the combination of enzalutamide and GSK-126 in CRPC, also offering new avenues for immunotherapy in prostate cancer.</p>","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11160446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140287244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EpigenomicsPub Date : 2024-03-21DOI: 10.2217/epi-2023-0403
Ye-Chen Qi, Hui Bai, Si-Le Hu, Shu-Juan Li, Qian-Zhong Li
{"title":"Coregulatory effects of multiple histone modifications in key ferroptosis-related genes for lung adenocarcinoma.","authors":"Ye-Chen Qi, Hui Bai, Si-Le Hu, Shu-Juan Li, Qian-Zhong Li","doi":"10.2217/epi-2023-0403","DOIUrl":"10.2217/epi-2023-0403","url":null,"abstract":"<p><p><b>Aim:</b> The present study was designed to investigate the coregulatory effects of multiple histone modifications (HMs) on gene expression in lung adenocarcinoma (LUAD). <b>Materials & methods:</b> Ten histones for LUAD were analyzed using ChIP-seq and RNA-seq data. An innovative computational method is proposed to quantify the coregulatory effects of multiple HMs on gene expression to identify strong coregulatory genes and regions. This method was applied to explore the coregulatory mechanisms of key ferroptosis-related genes in LUAD. <b>Results:</b> Nine strong coregulatory regions were identified for six ferroptosis-related genes with diverse coregulatory patterns (<i>CA9</i>, <i>PGD</i>, <i>CDKN2A</i>, <i>PML</i>, <i>OTUB1</i> and <i>NFE2L2</i>). <b>Conclusion:</b> This quantitative method could be used to identify important HM coregulatory genes and regions that may be epigenetic regulatory targets in cancers.</p>","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11160448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140179500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EpigenomicsPub Date : 2024-03-14DOI: 10.2217/epi-2023-0424
Barry M Lester, Marie Camerota, Todd M Everson, Coral L Shuster, Carmen J Marsit
{"title":"Toward a more holistic approach to the study of exposures and child outcomes.","authors":"Barry M Lester, Marie Camerota, Todd M Everson, Coral L Shuster, Carmen J Marsit","doi":"10.2217/epi-2023-0424","DOIUrl":"10.2217/epi-2023-0424","url":null,"abstract":"<p><p><b>Aim:</b> The current work was designed to demonstrate the application of the exposome framework in examining associations between exposures and children's long-term neurodevelopmental and behavioral outcomes. <b>Methods:</b> Longitudinal data were collected from birth through age 6 from 402 preterm infants. Three statistical methods were utilized to demonstrate the exposome framework: exposome-wide association study, cumulative exposure and machine learning models, with and without epigenetic data. <b>Results:</b> Each statistical approach answered a distinct research question regarding the impact of exposures on longitudinal child outcomes. Findings highlight associations between exposures, epigenetics and executive function. <b>Conclusion:</b> Findings demonstrate how an exposome-based approach can be utilized to understand relationships between internal (e.g., DNA methylation) and external (e.g., prenatal risk) exposures and long-term developmental outcomes in preterm children.</p>","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11157992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140119139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EpigenomicsPub Date : 2024-03-13DOI: 10.2217/epi-2023-0114
Shuzheng Zhang, Baoshan Ma, Yu Liu, Yiwen Shen, Di Li, Shuxin Liu, Fengju Song
{"title":"Predicting locus-specific DNA methylation levels in cancer and paracancer tissues.","authors":"Shuzheng Zhang, Baoshan Ma, Yu Liu, Yiwen Shen, Di Li, Shuxin Liu, Fengju Song","doi":"10.2217/epi-2023-0114","DOIUrl":"10.2217/epi-2023-0114","url":null,"abstract":"<p><p><b>Aim:</b> To predict base-resolution DNA methylation in cancerous and paracancerous tissues. <b>Material & methods:</b> We collected six cancer DNA methylation datasets from The Cancer Genome Atlas and five cancer datasets from Gene Expression Omnibus and established machine learning models using paired cancerous and paracancerous tissues. Tenfold cross-validation and independent validation were performed to demonstrate the effectiveness of the proposed method. <b>Results:</b> The developed cross-tissue prediction models can substantially increase the accuracy at more than 68% of CpG sites and contribute to enhancing the statistical power of differential methylation analyses. An XGBoost model leveraging multiple correlating CpGs may elevate the prediction accuracy. <b>Conclusion:</b> This study provides a powerful tool for DNA methylation analysis and has the potential to gain new insights into cancer research from epigenetics.</p>","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11158003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140109702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Construction of a prognostic model based on genome-wide methylation analysis of miRNAs for hepatocellular carcinoma.","authors":"Zhaoqi Shi, Xiaolong Liu, Duguang Li, Xiaoxiao Fan, Lifeng He, Daizhan Zhou, Hui Lin","doi":"10.2217/epi-2023-0365","DOIUrl":"10.2217/epi-2023-0365","url":null,"abstract":"<p><p><b>Aim:</b> Using the methylation level of miRNA genes to develop a prognostic model for patients with hepatocellular carcinoma (HCC). <b>Materials & methods:</b> least absolute shrinkage and selection operator and multivariate Cox regression analyses were performed to develop a prognostic model. One miRNA in the model was selected for verification. <b>Results:</b> A prognostic model was developed using eight miRNAs. The areas under the curve for predicting overall survival at 1, 3 and 5 years were 0.75, 0.81 and 0.81. miR-223 was found to be hypomethylated in 160 HCC tissues, and its methylation level was associated with Barcelona Clinic Liver Cancer stages and the prognosis of patients with HCC. <b>Conclusion:</b> The prognostic model based on miRNA methylation levels has the capability to partially forecast the prognosis of patients with HCC.</p>","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11160443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140109701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EpigenomicsPub Date : 2024-03-06DOI: 10.2217/epi-2023-0391
Junbin Peng, Haojie Li, Fang Tong, Jinlong Hu, Min Li, Gan Chen, Dongquan Liu, Jinshan Liu, Rui Wang, Hongyu Xu, Xuanxuan Li, Xinguo Zhong, Jiaming Yao, Baoqiang Cao
{"title":"Methylation changes of liver DNA during the formation of gallstones.","authors":"Junbin Peng, Haojie Li, Fang Tong, Jinlong Hu, Min Li, Gan Chen, Dongquan Liu, Jinshan Liu, Rui Wang, Hongyu Xu, Xuanxuan Li, Xinguo Zhong, Jiaming Yao, Baoqiang Cao","doi":"10.2217/epi-2023-0391","DOIUrl":"10.2217/epi-2023-0391","url":null,"abstract":"<p><p><b>Aim:</b> To explore the overall methylation changes in liver tissues during the formation of gallstones, as well as the key pathways and genes involved in the process. <b>Methods:</b> Reduced-representation bisulfite sequencing and RNA sequencing were conducted on the liver tissues of mice with gallstones and control normal mice. <b>Results:</b> A total of 8705 differentially methylated regions in CpG and 1410 differentially expressed genes were identified. The joint analysis indicated that aberrant DNA methylation may be associated with dysregulated gene expression in key pathways such as cholesterol metabolism and bile secretion. <b>Conclusion:</b> We propose for the first time that methylation changes in some key pathway genes in liver tissue may be involved in the formation of gallstones.</p>","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11160444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140039008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EpigenomicsPub Date : 2024-03-01Epub Date: 2024-02-27DOI: 10.2217/epi-2023-0357
Rosa Pardo V, Richard H Finnell, M Elizabeth Ross, Pablo Alarcón, José Suazo
{"title":"Neural tube defects and epigenetics: role of histone post-translational histone modifications.","authors":"Rosa Pardo V, Richard H Finnell, M Elizabeth Ross, Pablo Alarcón, José Suazo","doi":"10.2217/epi-2023-0357","DOIUrl":"10.2217/epi-2023-0357","url":null,"abstract":"<p><p>Neural tube defects (NTDs) are the most common congenital anomalies of the CNS. It is widely appreciated that both genetic and environmental factors contribute to their etiology. The inability to ascribe clear genetic patterns of inheritance to various NTD phenotypes suggests it is possible that epigenetic mechanisms are involved in the etiology of NTDs. In this context, the contribution of DNA methylation as an underlying contributing factor to the etiology of NTDs has been extensively reviewed. Here, an updated accounting of the evidence linking post-translational histone modifications to these birth defects, relying heavily upon studies in humans, and the possible molecular implications inferred from reports based on cellular and animal models, are presented.</p>","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"419-426"},"PeriodicalIF":3.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139971500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The study of <i>HMOX1</i> DNA methylation and gene expression and the diagnostic potential of <i>miR-153-3p</i> in preeclampsia.","authors":"Somayeh Rahimi, Nayebali Rezvani, Saeed Khazayel, Nazanin Jalilian, Ebrahim Shakiba, Fatemeh Khadir, Kheirollah Yari, Zohreh Rahimi","doi":"10.2217/epi-2023-0377","DOIUrl":"10.2217/epi-2023-0377","url":null,"abstract":"<p><p><b>Background:</b> The objective was to elucidate the potential epigenetic regulatory mechanism in <i>HMOX1</i> expression in preeclampsia. <b>Materials & methods:</b> <i>HMOX1</i> promoter DNA methylation was evaluated in the placental tissue and blood of preeclamptic and normotensive pregnant women. <i>HMOX1</i> and <i>miR-153-3p</i> gene expression were assessed in placental tissue and peripheral blood mononuclear cells (PBMCs). Related microarray datasets in the Gene Expression Omnibus database were also analyzed. <b>Results:</b> In placental tissue, despite <i>HMOX1</i> expression downregulation, there was no significant change in <i>HMOX1</i> methylation. In PBMCs, there was no significant alteration in <i>HMOX1</i> expression, while hypomethylation was observed in blood. The <i>miR-153-3p</i> expression increased in the placental tissue and in the PBMCs of preeclampsia. <b>Conclusion:</b> DNA methylation does not affect <i>HMOX1</i> expression, while <i>miR-153-3p</i> might be a biomarker for preeclampsia.</p>","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"389-401"},"PeriodicalIF":3.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139971501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Epigenetic disruption of histone deacetylase-2 accelerated apoptotic signaling and retarded malignancy in gastric cells.","authors":"Sayedeh Azimeh Hosseini, Mahdi Ghatrehsamani, Hajar Yaghoobi, Fatemeh Elahian, Seyed Abbas Mirzaei","doi":"10.2217/epi-2023-0350","DOIUrl":"10.2217/epi-2023-0350","url":null,"abstract":"<p><p><b>Background:</b> The objective of this research was to determine whether HDAC2 function is associated with gastric cancer progression. <b>Methods:</b> HDAC2 was knocked out in EPG85.257 cells using CRISPR/Cas9 and tumorigenesis pathways were evaluated. <b>Results:</b> Cell proliferation, colony formation, wound healing and transwell invasion were inhibited in ΔHDAC2:EPG85.257 cells. Quantitative analyses revealed a significant downregulation of MMP1, p53, Bax, MAPK1, MAPK3, pro-Caspase3, ERK1/2, p-ERK1/2, AKT1/2/3, p-AKT1/2/3, p-NF-κB (p65), Twist, Snail and p-FAK transcripts/proteins, while SIRT1, PTEN, p21 and Caspase3 were upregulated in ΔHDAC2:EPG85.257 cells. <b>Conclusion:</b> These results indicated that HDAC2 enhanced migration, colony formation and transmigration ability. HDAC2 inhibition may improve gastric cancer chemotherapy pathways.</p>","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"277-292"},"PeriodicalIF":3.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139734834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EpigenomicsPub Date : 2024-03-01Epub Date: 2024-02-15DOI: 10.2217/epi-2023-0339
Meisam Bagheri, Min Kyung Lee, Kristen E Muller, Todd W Miller, Diwakar R Pattabiraman, Brock C Christensen
{"title":"Alteration of DNA methyltransferases by eribulin elicits broad DNA methylation changes with potential therapeutic implications for triple-negative breast cancer.","authors":"Meisam Bagheri, Min Kyung Lee, Kristen E Muller, Todd W Miller, Diwakar R Pattabiraman, Brock C Christensen","doi":"10.2217/epi-2023-0339","DOIUrl":"10.2217/epi-2023-0339","url":null,"abstract":"<p><p><b>Background:</b> Triple-negative breast cancer (TNBC) is an aggressive disease with limited treatment options. Eribulin, a chemotherapeutic drug, induces epigenetic changes in cancer cells, suggesting a unique mechanism of action. <b>Materials & methods:</b> MDA-MB 231 cells were treated with eribulin and paclitaxel, and the samples from 53 patients treated with neoadjuvant eribulin were compared with those from 14 patients who received the standard-of-care treatment using immunohistochemistry. <b>Results:</b> Eribulin treatment caused significant DNA methylation changes in drug-tolerant persister TNBC cells, and it also elicited changes in the expression levels of epigenetic modifiers (DNMT1, TET1, DNMT3A/B) <i>in vitro</i> and in primary TNBC tumors. <b>Conclusion:</b> These findings provide new insights into eribulin's mechanism of action and potential biomarkers for predicting TNBC treatment response.</p>","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"293-308"},"PeriodicalIF":3.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10910603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139734833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}