Epigenomics最新文献

Aim: Using the methylation level of miRNA genes to develop a prognostic model for patients with hepatocellular carcinoma (HCC). Materials & methods: 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. Results: 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. Conclusion: The prognostic model based on miRNA methylation levels has the capability to partially forecast the prognosis of patients with HCC.

Aim: 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. Methods: Reduced-representation bisulfite sequencing and RNA sequencing were conducted on the liver tissues of mice with gallstones and control normal mice. Results: 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. Conclusion: 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.

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.

Background: The objective was to elucidate the potential epigenetic regulatory mechanism in HMOX1 expression in preeclampsia. Materials & methods: HMOX1 promoter DNA methylation was evaluated in the placental tissue and blood of preeclamptic and normotensive pregnant women. HMOX1 and miR-153-3p 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. Results: In placental tissue, despite HMOX1 expression downregulation, there was no significant change in HMOX1 methylation. In PBMCs, there was no significant alteration in HMOX1 expression, while hypomethylation was observed in blood. The miR-153-3p expression increased in the placental tissue and in the PBMCs of preeclampsia. Conclusion: DNA methylation does not affect HMOX1 expression, while miR-153-3p might be a biomarker for preeclampsia.

Background: The objective of this research was to determine whether HDAC2 function is associated with gastric cancer progression. Methods: HDAC2 was knocked out in EPG85.257 cells using CRISPR/Cas9 and tumorigenesis pathways were evaluated. Results: 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. Conclusion: These results indicated that HDAC2 enhanced migration, colony formation and transmigration ability. HDAC2 inhibition may improve gastric cancer chemotherapy pathways.

Background: 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. Materials & methods: 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. Results: 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) in vitro and in primary TNBC tumors. Conclusion: These findings provide new insights into eribulin's mechanism of action and potential biomarkers for predicting TNBC treatment response.

Background: To explore the role of fatty acid metabolism (FAM)-related lncRNAs in the prognosis and antitumor immunity of serous ovarian cancer (SOC). Materials & methods: A SOC FAM-related lncRNA risk model was developed and evaluated by a series of analyses. Additional immune-related analyses were performed to further assess the associations between immune state, tumor microenvironment and the prognostic risk model. Results: Five lncRNAs associated with the FAM genes were found and used to create a predictive risk model. The patients with a low-risk profile exhibited favorable prognostic outcomes. Conclusion: The established prognostic risk model exhibits better predictive capabilities for the prognosis of patients with SOC and offers novel potential therapy targets for SOC.

Aim: To explore the role of Piwi protein and piRNAs in DNMT3L-mediated epigenetic inheritance. Materials & methods: Transgenic Drosophila were used to examine the effect of ectopically expressed DNMT3L on the profile of piRNAs by sequencing of small RNAs. Results & conclusion: Our previous work showed accumulation and inheritance of epimutations across multiple generations in transgenic DNMT3L Drosophila. Here, we show interaction of DNMT3L with Piwi and a significant alteration in the piRNA profile across multiple generations in transgenic Drosophila. In the light of its interaction with histone H1, we propose that in addition to its role of modulating core histone modifications, DNMT3L allows for inheritance of epigenetic information through its collaboration with Piwi, piRNAs and histone H1.

Recent genomics and epigenetic advances have empowered the exploration of DNA/RNA methylation and histone modifications crucial for gene expression in response to stress, aging and disease. Interest in understanding neuronal plasticity's epigenetic mechanisms, influencing brain rewiring amid development, aging and neurodegenerative disorders, continues to grow. Histone acetylation dysregulation, a commonality in diverse brain disorders, has become a therapeutic focus. Histone acetyltransferases and histone deacetylases have emerged as promising targets for neurodegenerative disorder treatment. This review delves into histone acetylation regulation, potential therapies and future perspectives for disorders like Alzheimer's, Parkinson's and Huntington's. Exploring genetic-environmental interplay through models and studies reveals molecular changes, behavioral insights and early intervention possibilities targeting the epigenome in at-risk individuals.

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. The occurrence of CRC is associated with various genetic and epigenetic mutations in intestinal epithelial cells that transform them into adenocarcinomas. There is increasing evidence indicating the gut microbiota plays a crucial role in the regulation of host physiological processes. Alterations in gut microbiota composition are responsible for initiating carcinogenesis through diverse epigenetic modifications, including histone modifications, ncRNAs and DNA methylation. This work was designed to comprehensively review recent findings to provide insight into the associations between the gut microbiota and CRC at an epigenetic level. These scientific insights can be used in the future to develop effective strategies for early detection and treatment of CRC.