Gene最新文献

{"title":"Single nuclear RNA sequencing and analysis of basal cells in pulmonary acute respiratory distress syndrome.","authors":"Haoran Chen, Xiaobing Chen, Jinqiu Ding, Haoyue Xue, Xinyi Tang, Xiaomin Li, Yongpeng Xie","doi":"10.1016/j.gene.2024.149131","DOIUrl":"10.1016/j.gene.2024.149131","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to find the gene expression profile specifically in basal cells from pulmonary acute respiratory distress syndrome (ARDSp) patients using single-cell level analysis.</p><p><strong>Methods: </strong>Single nuclear RNA sequencing (snRNA-seq) data of lung samples, including 18 ARDSp participants and 7 healthy participants, were sourced from the GEO database (GSE171524). The differentially expressed genes (DEGs) were screened by | log2FC | >1 and P < 0.05. Functional enrichment was constructed via Gene Ontology (GO) analysis. Pathway enrichment was conducted via Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The protein-protein interaction (PPI) network of the DEGs was performed via the STRING database. Cytoscape software was employed to find hub genes. The hub genes were sequenced and validated via data set after constructing the rat model of ARDSp.</p><p><strong>Results: </strong>Using DESeq2 package, 299 genes were disclosed to be downregulated, while 228 were upregulated in ARDSp participants. GO analysis disclosed DEGs were enriched in processes like actin filament organization, regulation of small GTPase-mediated signal transduction, response to unfolded protein, wound healing, and response to oxygen levels. Meanwhile, KEGG analysis disclosed DEGs were involved in protein digestion and absorption, Th17 cell differentiation, iron death, and other biological effects. Ten hub genes, including FN1, HIF1A, HSP90AA1, SMAD3, FOS, CDKN2A, COL1A1, HSPA8, FLNA, and NFKBIA were highlighted based on their network centrality and biological significance. HIF1A, HSPA8, NFKBIA, and CDKN2A were differentially expressed in the validation dataset.</p><p><strong>Conclusions: </strong>Basal cells in ARDSp exhibit significant changes in gene expression, with ten hub genes identified. Among them, four (HIF1A, HSPA8, NFKBIA, CDKN2A) were validated experimentally using RNA-Seq data from an ARDSp rat model. This study emphasizes the role of basal cells in ARDSp, highlighting the altered gene networks involved in repair and inflammatory responses, providing potential targets for further therapeutic exploration. These findings suggest that alterations in these hub genes may be crucial to basal cell-driven inflammatory and reparative responses in ARDSp.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"936 ","pages":"149131"},"PeriodicalIF":2.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Regulation of cell proliferation and migration in gallbladder cancer by zinc finger X-chromosomal protein\" [528(2) (2013) 261-266].","authors":"Zhujun Tan, Shenglai Zhang, Maolan Li, Xiangsong Wu, Hao Weng, Qian Ding, Yang Cao, Runfa Bao, Yijun Shu, Jiasheng Mu, Qichen Ding, Wenguang Wu, Jiahua Yang, Lin Zhang, Yingbin Liu","doi":"10.1016/j.gene.2024.149113","DOIUrl":"10.1016/j.gene.2024.149113","url":null,"abstract":"","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149113"},"PeriodicalIF":2.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early life lipid overload in Native American Myopathy is phenocopied by stac3 knockout in zebrafish.","authors":"Rajashekar Donaka, Houfeng Zheng, Cheryl L Ackert-Bicknell, David Karasik","doi":"10.1016/j.gene.2024.149123","DOIUrl":"10.1016/j.gene.2024.149123","url":null,"abstract":"<p><p>Understanding the early stages of human congenital myopathies is critical for proposing strategies for improving musculoskeletal muscle performance, such as restoring the functional integrity of the cytoskeleton. SH3 and cysteine-rich domain 3 (STAC3) are proteins involved in nutrient regulation and are an essential component of the excitation-contraction (EC) coupling machinery for Ca²⁺ releasing. A mutation in STAC3 causes debilitating Native American Myopathy (NAM) in humans, while loss of this gene in mice and zebrafish (ZF) results in premature death. Clinically, NAM patients demonstrated increased lipids in skeletal muscle, but it is unclear if neutral lipids are associated with altered muscle function in NAM. Using a CRISPR/Cas9 induced stac3^-/- knockout (KO) zebrafish model, we determined that loss of stac3 leads to delayed larval hatching which corresponds with muscle weakness and decreased whole-body Ca²⁺ level during early skeletal development. Specifically, we observed defects in the cytoskeleton in F-actin and slow muscle fibers at 5 and 7 days post-fertilizations (dpf). Myogenesis regulators such as myoD and myf5, mstnb were significantly altered in stac3^-/- larvae. These muscle alterations were associated with elevated neutral lipid levels starting at 5 dpf and persisting beyond 7 dpf. Larva lacking stac3 had reduced viability with no larva knockouts surviving past 11 dpf. This data suggests that our stac3^-/- zebrafish serve as an alternative model to study the diminished muscle function seen in NAM patients. The data gathered from this new model over time supports a mechanistic view of lipotoxicity as a critical part of the pathology of NAM and the associated loss of function in muscle.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149123"},"PeriodicalIF":2.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142727577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"c.640-814T>C mutation in deep intronic region of alpha-galactosidase A gene is associated with Fabry disease via dominant-negative effect.","authors":"Piyi Zhang, Yongxiang Wang, Gaxue Jiang, Yiming Zhang, Yonglin Chen, Yu Peng, Zixian Chen, Ming Bai","doi":"10.1016/j.gene.2024.149127","DOIUrl":"10.1016/j.gene.2024.149127","url":null,"abstract":"<p><p>Fabry disease (FD) is a lysosomal storage disorder resulting from mutations in the alpha-galactosidase A (GLA) gene, characterized by pain, skin lesions, renal failure, and cardiac disease. A 60-year-old proband was hospitalized for recurrent atrial fibrillation (AF) that was unresponsive to medication, with cardiac magnetic resonance imaging (CMRI) revealing left ventricular wall hypertrophy and fat infiltration. Whole-exome sequencing (WES) did not reveal any suspicious pathogenic variants. To further assess the diagnosis, endomyocardial biopsy (EMB) and electron microscopy were performed, revealing abundant zebra bodies in cardiomyocytes, consistent with FD. The diagnosis was ultimately confirmed by GLA enzyme activity analysis (<1.00). Further genetic investigations identified a deep intronic variant (c.640-814T>C) within the GLA gene. Minigene experiments demonstrated that this variant affected the splicing of GLA, resulting in the production of a truncated protein (p.Pro214SerfsTer10). Western blotting (WB) showed that the truncated protein was retained, while immunofluorescence (IF) analysis indicated partial lysosomal localization. In vitro assays confirmed that the retained protein was non-functional and exerted a dominant-negative effect on the normal GLA protein. Molecular docking analysis further revealed that the truncated protein could bind to the wild GLA monomer, significantly reducing cellular GLA enzyme activity. These findings indicate that, beyond being non-functional, the c.640-814T>C mutation may also exerts a dominant-negative effect that impairs the function of the wild GLA protein. These results highlight the importance of recognizing deep intronic mutations in the diagnosis and treatment of FD, contributing to a deeper understanding of the molecular mechanisms, enriching mutation databases, and providing insights into genotype-phenotype correlations.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149127"},"PeriodicalIF":2.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic analysis of key genes and signaling pathways in sepsis-associated intestinal mucosal barrier damage.","authors":"Zhao Gao, Zhiyuan Gong, Hai Huang, Xuemeng Ren, Zhenlu Li, Peng Gao","doi":"10.1016/j.gene.2024.149137","DOIUrl":"10.1016/j.gene.2024.149137","url":null,"abstract":"<p><strong>Objectives: </strong>The aim is to analyze differentially expressed genes (DEGs) in mice with sepsis-related intestinal mucosal barrier damage and to explore the diagnostic and protective mechanisms of this condition at the transcriptome level.</p><p><strong>Methods: </strong>Small intestinal tissues from healthy male C57BL/6J mice subjected to Cecal ligation and puncture (CLP) and sham operation were collected. High-throughput sequencing was performed using the paired-end sequencing mode of the Illumina HiSeq platform. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted on the differentially expressed genes (DEGs). A protein-protein interaction (PPI) network was constructed using the STRING database, and hub genes were identified with Cytoscape. These hub genes were then validated using quantitative real-time polymerase chain reaction (RT-qPCR).</p><p><strong>Results: </strong>A total of 239 DEGs were identified, with 49 upregulated and 130 downregulated genes. KEGG enrichment analysis showed that these DEGs were primarily involved in cytokine-cytokine receptor interaction, Th1 and Th2 cell differentiation, viral protein interactions with cytokines and their receptors, and the IL-17 signaling pathway. The top 10 hub genes were selected using the cytoHubba plugin. Experimental validation confirmed that the expression levels of TBX21, CSF3, IL-6, CXCR3, and CXCL9 matched the sequencing results.</p><p><strong>Conclusion: </strong>TBX21, CSF3, IL-6,CXCR3, and CXCL9 may be potential biological markers for the diagnosis and treatment the sepsis-associated intestinal mucosal barrier.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"936 ","pages":"149137"},"PeriodicalIF":2.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Transcriptome analysis to identify key genes involved in terpenoid and rosmarinic acid biosynthesis in lemon balm (Melissa officinalis)\" [Gene 773 (2021) 145417].","authors":"Mehdi Mansouri, Fatemeh Mohammadi","doi":"10.1016/j.gene.2024.149114","DOIUrl":"10.1016/j.gene.2024.149114","url":null,"abstract":"","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149114"},"PeriodicalIF":2.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analyses of biosynthesis mutants reveal that the fifth and sixth sugars of the Porphyromonas gingivalis O-glycan are L-fucose and N-acetylgalactosamine respectively.","authors":"Mikio Shoji, Eric C Reynolds, Paul D Veith","doi":"10.1016/j.gene.2024.149182","DOIUrl":"https://doi.org/10.1016/j.gene.2024.149182","url":null,"abstract":"<p><p>The oral pathogen, Porphyromonas gingivalis has a general O-glycosylation system which it utilises to modify hundreds of proteins localised outside of the periplasm. The O-glycan is a heptasaccharide that includes a putative L-fucose and N-acetylgalactosamine (GalNAc) as the 5th and 6th sugar residues respectively. The putative L-fucose is expected to be synthesized as GDP-L-fucose involving the enzymes Gmd (PGN_1078) and Fcl (PGN_1079), while GalNAc is putatively epimerised from GlcNAc by GalE (PGN_1614). In this study we created mutants lacking each of these three enzymes and analysed the resultant glycosylation defects. Immunoblot analysis using antibodies against the model glycoproteins Mfa2, PGN_0742 and PGN_1037 detected bands of reduced size, consistent with glycan truncation. Mass spectrometry analysis of tryptic digests of whole cell lysate proteins revealed that O-glycans in the galE mutant were predominantly pentasaccharides consistent with the 6th sugar being GalNAc. For the gmd and fcl mutants, tetrasaccharides were observed confirming the 5th sugar as L-fucose. The confirmation of these sugars also confirmed PGN_1135 as a GalNAc transferase as the previously analysed PGN_1135 mutant produced the same O-glycan truncation as the galE mutant.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149182"},"PeriodicalIF":2.6,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysing the relevance of TGF-β and its regulators in cervical cancer to identify therapeutic and diagnostic markers.","authors":"Jayapradha Gnanagurusamy, Sneha Krishnamoorthy, Bharathi Muruganatham, Selvamurugan Nagarajan, Sridhar Muthusami","doi":"10.1016/j.gene.2024.149166","DOIUrl":"https://doi.org/10.1016/j.gene.2024.149166","url":null,"abstract":"<p><p>The role of transforming growth factor-beta (TGF-β) is dual, such that, it inhibits tumor development in initial stage and promotes metastasis in later stage. The present study is aimed to analyse the relevance of different types of TGF-β and their receptors on the overall survival (OS) and TGF-β driven gene expression in individuals with cervical cancer (CC) using ONCODB and GEPIA databases. The in-silico gene expression analysis showed, TGF-β1 and TGFβR2 are upregulated in cells infected with human papilloma virus (HPV)16, whereas, TGF-β2, TGFβR1 and TGFβR3 expression were downregulated. In HPV 18 infected cells, TGF-β1, TGF-β2 and TGFβR1 were downregulated, meanwhile, TGF-β3, TGFβR2 and TGFβR3 were upregulated. OS analysis of CC patients with different TGF-β expression revealed that, TGF-β1, TGF-β2, TGF-β3 and TGFβR2 were associated with reduced survival rate. Further, we identified four microRNAs (miRNAs) (hsa-miR-21-5p, hsa-miR-29b-3p, hsa-miR-101-3p and hsa-miR-130a-3p) interacted favorably with TGF-β in HPV 16 and 18 positive samples using MIENTURNET. This present review further emphasizes that, targeting TGF-β could be a novel and futuristic approach for CC management and therapeutics.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149166"},"PeriodicalIF":2.6,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The physiological and molecular mechanisms of WRKY transcription factors regulating drought tolerance: A review.","authors":"Meiran Li, Zhenquan Duan, Shengzhong Zhang, Jiancheng Zhang, Jing Chen, Hui Song","doi":"10.1016/j.gene.2024.149176","DOIUrl":"10.1016/j.gene.2024.149176","url":null,"abstract":"<p><p>WRKY transcription factors (TFs) play crucial roles in responses to abiotic and biotic stresses that significantly impact plant growth and development. Advancements in molecular biology and sequencing technologies have elevated WRKY TF studies from merely determining expression patterns and functional characterization to uncovering molecular regulatory networks. Numerous WRKY TFs regulate drought tolerance in plants through various regulatory networks. This review details the physiological and molecular mechanisms of WRKY TFs regulating drought tolerance. The review focuses on the WRKY TFs involved in the phytohormone and metabolic pathways associated with the drought stress response and the multiple functions of these WRKY TFs, including biotic and abiotic stress responses and their participation in plant growth and development.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149176"},"PeriodicalIF":2.6,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning and multi-omics characterization of SLC2A1 as a prognostic factor in hepatocellular carcinoma: SLC2A1 is a prognostic factor in HCC.","authors":"Kangjie Xu, Houliang Zhang, Hua Dai, Weipu Mao","doi":"10.1016/j.gene.2024.149178","DOIUrl":"10.1016/j.gene.2024.149178","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is characterized by high incidence, significant mortality, and marked heterogeneity, making accurate molecular subtyping essential for effective treatment. Using multi-omics data from HCC patients, we applied diverse clustering algorithms to identify three HCC subtypes (HSs) with distinct prognostic characteristics. Among these, HS1 emerged as an immune-compromised subtype associated with the poorest prognosis. Additionally, we developed a novel, robust, and highly accurate machine learning-guided prognostic signature (MLPS) by integrating multiple machine learning algorithms and their combinations. Our study also identified SLC2A1, the core gene of MLPS, as being highly expressed during advanced stages of tumor progression. Knockdown experiments demonstrated that reducing SLC2A1 expression significantly suppressed the malignant behavior of HCC cells. Furthermore, SLC2A1 expression was linked to responsiveness to dasatinib and vincristine, suggesting potential therapeutic relevance. MLPS and SLC2A1 offer promising tools for individualized prognosis prediction and targeted therapy in HCC, providing new opportunities to improve patient outcomes.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149178"},"PeriodicalIF":2.6,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142835157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}