Current Genomics - Online First
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Integrated Multi-omics Analysis of Hub Genes and miRNA Interactions in Hypertrophic Cardiomyopathy
Authors: Huanhuan Hu, Ziheng Yu, Kongjie Lu, Hui Hu and Lang DengAvailable online: 26 March 2025More LessBackgroundHypertrophic Cardiomyopathy (HCM) is a complex cardiac disorder marked by the thickening of the heart muscle.
MethodHCM and normal control cell lines were cultured in DMEM with 12.5% FBS and 1% penicillin-streptomycin at 37°C and 5% CO2. Differentially expressed genes (DEGs) were identified from GSE32453, GSE53408, and GSE113439 datasets using the limma package in R. Hub genes were determined through protein-protein interaction (PPI) network and Cytoscape analysis and validated via Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) and Western blot analysis. Gene enrichment, miRNA predictions, drug prediction, and molecular docking analyses were conducted for functional enrichment and to explore hub gene-associated drugs.
ResultsTo identify DEGs and hub genes implicated in HCM, we analyzed three Gene Expression Omnibus (GEO) datasets (GSE32453, GSE53404, and GSE1134439), extracting the top 1000 DEGs. Venn analysis revealed 21 common down-regulated genes. PPI analysis identified these six as key hub genes, including Iron Response Element Binding Protein 2 (IREB2), Protein Tyrosine Phosphatase, Non-Receptor Type 11 (PTPN11), IQ Motif Containing GTPase Activating Protein 1 (IQGAP1), Phosphoglucomutase 2 (PGM2), DIS3 RNA Exonuclease 3' to 5' (DIS3), Glutamine-Fructose-6-Phosphate Transaminase 1 (GFPT1) in HCM patients. Gene enrichment analysis highlighted the involvement of these genes in cellular functions such as energy metabolism and growth factor signaling, suggesting their role in the disease's progression. Validation using an additional dataset (GSE36961) confirmed significant down-regulation of all hub genes in HCM samples, supported by Receiver Operating Characteristic (ROC) curve analysis that demonstrated their diagnostic potential. Furthermore, miRNA analysis identified six up-regulated miRNAs (miR-124, miR-29b, miR-330, miR-34a, miR-375, and miR-451) that likely contribute to the dysregulation of these hub genes. Drug prediction analysis identified various potential therapeutic compounds targeting these hub genes. Molecular docking revealed favorable binding affinities, supporting the therapeutic potential of these drugs in modulating hub gene activity.
ConclusionOur findings suggest that IREB2, PTPN11, IQGAP1, PGM2, DIS3, and GFPT1 hub genes and their associated regulatory pathways may serve as biomarkers and therapeutic targets for HCM, potentially improving diagnosis and treatment strategies.
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Characterization and Genomic Analysis of Arthrobacter sp. SF27: A Promising Dibutyl Phthalate-degrading Strain
Authors: Ekaterina Korsakova, Yulia Nechaeva, Elena Plotnikova and Olga YastrebovaAvailable online: 14 March 2025More LessBackgroundPhthalic acid esters (PAEs) are widely used chemical compounds in various industries. However, PAEs are also a major source of pollution in soil and aquatic ecosystems, posing a significant environmental threat. Microbial degradation is a very effective way to remove phthalic acid esters from a polluted environment.
ObjectivesThe aims of this study were to investigate the ability of the strain Arthrobacter sp. SF27 (=VKM Ac-2063) to degrade PAEs (specifically, dibutyl phthalate (DBF)); to annotate the complete genome of the strain SF27 (GenBank accession number GCA_012952295); to identify genes (gene clusters) potentially involved in the degradation of DBF and its major degradation product, phthalic acid (PA).
MethodsThe ability of the strain SF27 to use DBP as the only source of carbon and energy was determined by cultivating it on a mineral medium containing 0.5–4 g/L DBP. The evaluation of the bacterial decomposition of DBP was carried out by GC-MS. The genome was annotated using the JGI Microbial Genome Annotation Pipeline (MGAP) (https://jgi.doe.gov/). Functional annotation was performed using various databases: KEGG, COG, NCBI, and GO. The Mauve program was used to compare the strain SF27 genome and the genomes of the closest DBP-degrading strains.
ResultsThe strain Arthrobacter sp. SF27 is capable of growing on DBP as the sole source of carbon and energy at high concentrations (up to 4 g/L). The strain was able to degrade 60% of DBP (initial concentration of 1 g/L) and 20% of DBP (initial concentration of 3 g/L) within 72 hours. The genome analysis of the strain SF27 (GenBank accession number GCA_012952295) identified genes encoding hydrolases potentially involved in the initial stages of DBP degradation, leading to the formation of PA. Additionally, a cluster of pht genes encoding enzymes that are responsible for the transformation of PA into protocatechuic acid (PCA) has been identified and described in the genome. Based on genome analysis and cultural experiments, a complete pathway for the degradation of PA by the strain Arthrobacter sp. SF27 into basal metabolic compounds of the cell has been proposed.
ConclusionBased on the conducted research, it can be stated that the strain Arthrobacter sp. SF27 is an efficient degrader of DBP, promising for the development of biotechnologies aimed at the restoration of ecosystems contaminated with DBP.
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DNMT3A Deficiency Reduces DNMT3B Gene Methylation and Contributes to Whole-genome Transcription Alterations in HEK293 Cells
Authors: Mengxiao Zhang, Jiaxian Wang, Gen Qi, Lanfeng Xie, Qiuxiang Tian, Hui Yang, Lei Feng, Nan Zhu, Xingchen Pan, Jianwei Zhu, Jianjun Hu, Peng Chen and Huili LuAvailable online: 24 February 2025More LessIntroductionDNA methylation is an important epigenetic modification associated with transcriptional repression and plays key roles in normal cell growth as well as oncogenesis. Among the three main DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B), DNMT3A mediates de novo DNA methylation. However, the general effect of DNMT3A on cell proliferation, metabolism, and downstream gene regulation is still to be unveiled.
MethodsIn this study, we successfully created DNMT3A-deficient HEK293 cells with frameshift mutations in the catalytic domain using CRISPR/Cas9 technology. The DNMT3A deficient cells showed a 21.5% reduction in global DNA methylation levels, leading to impaired cell proliferation as well as a blockage of MAPK and PI3K-Akt pathways in comparison with wild-type cells.
ResultsRNA-seq analysis demonstrated that DNMT3A knockout resulted in the up-regulation of genes and pathways related to cell metabolism but down-regulation of those involved in ribosome function, potentially explaining the growth and signaling pathways inhibition. Furthermore, DNMT3A ablation reduced DNMT3B gene methylation, explaining the down-regulated profiles of genes.
ConclusionOur findings suggest a complex epigenetic regulatory role for DNMT3A, and the compensatory upregulation of DNMT3B in response to DNMT3A deficiency warrants further investigation to be validated in future studies.
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