Epigenomics最新文献

Aim: The epigenome influences gene regulation and phenotypes in response to exposures. Epigenome assessment can determine exposure history aiding in diagnosis.Materials & methods: Here we developed and implemented a machine learning algorithm, the exposure signature discovery algorithm (ESDA), to identify the most important features present in multiple epigenomic and transcriptomic datasets to produce an integrated exposure signature (ES).Results: Signatures were developed for seven exposures including Staphylococcus aureus, human immunodeficiency virus, SARS-CoV-2, influenza A (H3N2) virus and Bacillus anthracis vaccinations. ESs differed in the assays and features selected and predictive value.Conclusion: Integrated ESs can potentially be utilized for diagnosis or forensic attribution. The ESDA identifies the most distinguishing features enabling diagnostic panel development for future precision health deployment.

Aim: To investigate function of somatostatin receptor 5 antisense RNA 1 (SSTR5-AS1) in esophageal carcinoma (ESCA).Materials & methods: The cellular function was assessed using EdU staining and Transwell assay. The localization of SSTR5-AS1 was measured using fluorescence in situ hybridization staining.Results: SSTR5-AS1 shRNA repressed invasion and migration and induced apoptosis in ESCA cells. SSTR5-AS1 was distributed in cytoplasm, and it regulated its subunit integrin beta 6 (ITGB6) via eukaryotic translation initiation factor 4A3 (EIF4A3). SSTR5-AS1 shRNA inactivated ITGB6 and JAK1/STAT3 signaling. SSTR5-AS1 silencing attenuated the malignant behavior of ESCA cells through the ITGB6-mediated JAK1/STAT3 axis.Conclusion: SSTR5-AS1 promotes tumorigenesis of ESCA by interacting with EIF4A3 to regulate ITGB6/JAK1/STAT3 axis, which serves a basis for discovering strategies against ESCA.

Aim: Methylation of LDLR, PCSK9 and LDLRAP1 CpG sites was assessed in patients with familial hypercholesterolemia (FH). Methods: DNA methylation of was analyzed by pyrosequencing in 131 FH patients and 23 normolipidemic (NL) subjects.Results:  LDLR, PCSK9 and LDLRP1 methylation was similar between FH patients positive (MD) and negative (non-MD) for pathogenic variants in FH-related genes. LDLR and PCSK9 methylation was higher in MD and non-MD groups than NL subjects (p < 0.05). LDLR, PCSK9 and LDLRAP1 methylation profiles were associated with clinical manifestations and cardiovascular events in FH patients (p < 0.05).Conclusion: Differential methylation of LDLR, PCSK9 and LDLRAP1 is associated with hypercholesterolemia and cardiovascular events. This methylation profile maybe useful as a biomarker and contribute to the management of FH.

Aim: This is a brief description of links between nine epigenetic clocks related to human aging and socioeconomic and behavioral characteristics as well as health outcomes.Materials & methods: We estimate frequently used and novel clocks from one data source, the Health and Retirement Study.Results: While all of these clocks are thought to reflect "aging," they use different CpG sites and do not strongly relate to each other. First and fourth generation clocks are not as linked to socioeconomic status or health outcomes as second and third generation clocks.Conclusion: Epigenetic clocks reflect exciting new tools and their continued evolution is likely to improve our understanding of how exposures get under the skin to accelerate aging.

Aim: This study investigates the altered expression and CpG methylation patterns of histone demethylase KDM8 in hepatocellular carcinoma (HCC), aiming to uncover insights and promising diagnostics biomarkers.Materials & methods: Leveraging TCGA-LIHC multi-omics data, we employed R/Bioconductor libraries and Cytoscape to analyze and construct a gene correlation network, and LASSO regression to develop an HCC-predictive model.Results: In HCC, KDM8 downregulation is correlated with CpGs hypermethylation. Differential gene correlation analysis unveiled a liver carcinoma-associated network marked by increased cell division and compromised liver-specific functions. The LASSO regression identified a highly accurate HCC prediction signature, prominently featuring CpG methylation at cg02871891.Conclusion: Our study uncovers CpG hypermethylation at cg02871891, possibly influencing KDM8 downregulation in HCC, suggesting these as promising biomarkers and targets.

Single-cell sequencing technologies enhance our understanding of cellular dynamics throughout pregnancy. We outlined the workflow of single-cell sequencing techniques and reviewed single-cell studies in maternal and child health. We conducted a literature review of single cell studies on maternal and child health using PubMed. We summarized the findings from 16 single-cell atlases of the human and mammalian placenta across gestational stages and 31 single-cell studies on maternal exposures and complications including infection, obesity, diet, gestational diabetes, pre-eclampsia, environmental exposure and preterm birth. Single-cell studies provides insights on novel cell types in placenta and cell type-specific marks associated with maternal exposures and complications.

Necroptosis is a novel form of cell death which is activated when apoptotic cell death signals are disrupted. Accumulating body of observations suggests that noncoding RNAs, which are the lately discovered mystery of the human genome, are significantly associated with necroptotic signaling circuitry. The fate and function of miRNAs have been well documented in human disease, especially cancer. Recently, lncRNAs have gained much attention due to their diverse regulatory functions. Although available studies are currently based on bioinformatic analysis, predicted interactions desires further attention, as these hold significant promise and should not be overlooked. In the light of these, here we comprehensively review and discuss noncoding RNA molecules that play significant roles during execution of necroptotic cell death.

Aim: This study explores Sevoflurane (Sevo)-induced neurotoxicity mechanisms in neonates through transcriptome sequencing and models.Methods: Seven-day-old mice were exposed to 3% Sevo, and hippocampal tissue was collected for analysis of differentially expressed lncRNAs and mRNAs compared with normal mice. MiR-152-3p was selected, and the interaction between H19, USP30, and miR-152-3p was explored in BV2 microglial cells and mouse hippocampal neurons.Results: Sevo disrupts mitochondrial autophagy via USP30 upregulation, exacerbating neurotoxicity and activating NLRP1 inflammasome-mediated inflammation.Conclusion: Sevo neurotoxicity is mediated through the H19/miR-152-3p/USP30 axis, implicating microglial regulation of neuronal pyroptosis.

Aim: To explore the LTBP4's expression, prognostic significance and molecular mechanism of action in breast cancer (BC).Methods: On the basis of omics datasets and experiments, we conducted a synthetical analysis of LTBP4 in BC.Results & conclusion: LTBP4 was downregulated in BC with high promoter methylation and low genetic alteration. DNA methylation was negatively associated with LTBP4 mRNA expression. Higher LTBP4 associated with better survival. LTBP4 was enrichment in extracellular matrix receptor interactions, cell adhesion molecules, cell cycle and MAPK pathway. LTBP4 expression and methylation were positively and negatively associated with tumor infiltrating immune cells, respectively. In conclusion, LTBP4 is a putative tumor suppressor in BC, which expression is regulated by DNA methylation and relates with prognosis.