Gene最新文献

The combination of transcriptional profiling and genotype data analyses enables the identification of genetic variants that may affect gene expression (eQTL - expression quantitative trait loci). This study aimed to identify cis-eQTL in Nellore cattle muscle tissue and determine their biological processes related to the immune system and involved eGenes. Genotypic data (SNP-Chip) and gene expression data (RNA-Seq) from a commercial population of 80 Nellore animals were evaluated. For the cis-eQTL identification, association tests were conducted for all variants near the gene (cis variants), followed by permutation tests to correct for multiple comparisons. Our analyses revealed 828 top cis-eQTL related to 1,062 genes of which most of these variants were in intronic and intergenic regions. The eQTLs rs109525554, rs109589165, rs110192253, rs133127698, rs137742430, rs41803313, rs43366333, and rs43711242 were associated with susceptibility and resistance to infections in cattle. Additionally, interferon family eGenes, such as IFNT3, IFN-TAU, IFNK, FYN, and IFNW1, and endothelial leukocyte migration, such as PRKCG and CXCL10 were found. These eGene families were linked to biological processes of innate and adaptive immune responses and associated with somatic cell scores in cattle, respectively. Our results may have implications for selecting desirable resistance traits in animals bred for production and highlight the importance of studying genetic variants involved in quantitative traits to improve our understanding of genetic mechanisms underlying gene expression regulation of adaptive traits in cattle.

Colorectal cancer (CRC) represents a common type of carcinoma with significant mortality rates globally. A primary factor contributing to the unfavorable treatment outcomes and reduced survival rates in CRC patients is the occurrence of metastasis. Various intricate molecular mechanisms are implicated in the metastatic process, leading to mortality among individuals with CRC. In the realm of intercellular communication, exosomes, which are a form of extracellular vesicle (EV), play an essential role. These vesicles act as conduits for information exchange between cells and originate from multiple sources. By fostering a microenvironment conducive to CRC progression, exosomes and EVs significantly influence the advancement of the disease. They contain a diverse array of molecules, including messenger RNAs (mRNAs), non-coding RNAs (ncRNAs), proteins, lipids, and transcription factors. Notably, ncRNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are prominently featured within exosomes. These ncRNAs have the capacity to regulate various critical molecules or signaling pathways, particularly those associated with tumor metastasis, thereby playing a crucial role in tumorigenesis. Their presence indicates a substantial potential to affect vital aspects of tumor progression, including proliferation, metastasis, and resistance to treatment. This research aims to categorize exosomal ncRNAs and examine their functions in colorectal cancer. Furthermore, it investigates the clinical applicability of novel biomarkers and therapeutic strategies in CRC. Abbreviations: ncRNAs, non-coding RNAs; CRC, Colorectal cancer; EV, extracellular vesicle; mRNAs, messenger RNAs; miRNAs, microRNAs; lncRNAs, long non-coding RNAs; circRNAs, circular RNAs; HOTTIP, HOXA transcript at the distal tip; NSCLC, non-small cell lung cancer; 5-FU, 5-fluorouracil; OX, Oxaliplatin; PDCD4, programmed cell death factor 4; Tregs, regulatory T cells; EMT, epithelial-mesenchymal transition; PFKFB3, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3; USP2, ubiquitin carboxyl-terminal hydrolase 2; TNM, tumor node metastasis; TAMs, tumor-associated macrophages; RASA1, RAS p21 protein activator 1; PDCD4, programmed cell death 4; ZBTB2, zinc finger and BTB domain containing 2; SOCS1, suppressor of cytokine signaling 1; TUBB3, β-III tubulin; MSCs, mesenchymal stem cells.

Peroxisome proliferator-activated receptor alpha (PPARα) plays a crucial role in regulating hepatic fat oxidation. Previous studies have identified VNN2 as a potential PPARα target gene in chicken liver. However, the specific function of VNN2 in hepatic lipid metabolism remains unclear. We utilized datasets GSM5764402, GSM5764403, GSE128340, GSE129840, and PRJEB44038 to investigate the expression pattern and potential function of VNN2 in chicken liver. Our analysis included RNA sequencing, qPCR, and triglyceride and total cholesterol assays for verification. Through analysis of single-cell RNA sequencing (scRNA-seq) data, we localized VNN2 expression at the cellular level and identified potential downstream targets of VNN2. We further examined these potential targets in VNN2 overexpressed and knockdown Leghorn male hepatoma (LMH) cells. Our findings revealed that VNN2 is highly expressed in hepatocytes with elevated lipid metabolism and steroid biosynthesis activity. This study confirms that VNN2 promotes steroid biosynthesis by upregulating MSMO1 and FDPS, providing new insights into its role in hepatic lipid metabolism.

Glutaminyl-peptide cyclotransferase-like protein (QPCTL) is a newly discovered enzyme that has sparked interest owing to its possible role in cancer genesis and progression. Initially discovered as a post-translational modification regulator of protein maturation, QPCTL has emerged as a key participant in cancer biology. Recent research has linked QPCTL to numerous essential cancer-related processes, including cell proliferation, migration, invasion, and apoptosis. Furthermore, QPCTL expression changes have been seen in a variety of cancer types, underlining its potential as a diagnostic and prognostic marker. The molecular mechanisms behind QPCTL's participation in cancer will be examined in this review. We investigate its involvement in the control of signaling pathways and the modification of cellular activities that are important in cancer. We also examine the clinical importance of QPCTL, including as its relationship with tumor development, metastasis, and response to treatment. We also discuss the possible therapeutic implications of targeting QPCTL in cancer therapy. QPCTL is a prospective target for the development of innovative anticancer treatments due to its participation in several cancer-associated pathways.

Aspergillus species produce polyketides, which form the basis of aflatoxins, some of the most significant mycotoxins in agriculture. Aflatoxins contaminate cereals, oilseeds, and nuts, both in the field and during storage. Of the 13 naturally occurring aflatoxins, the most potent are aflatoxins B₁, B₂, G₁, and G₂. The primary aflatoxigenic species are A. flavus, A. parasiticus, and A. nomius, while A. arachidicola, A. minisclerotigenes, and A. saccharicola also documented. These aflatoxin producers belong to three sections- 'Flavi', 'Ochraceorosei', and 'Nidulantes.' Aspergillus flavus, within section Flavi, shows morphological diversity, classified into Group I (S- and L- strains) and Group II (S- strains), with S-strains producing higher levels of aflatoxins. Aflatoxin biosynthesis is primarily regulated by the aflR gene, though other genes like aflS, aflP, aflQ, aflC, and aflM are also associated. However, presence of the aflR gene does not guarantee aflatoxin production across species. Sterigmatocystin serves as a precursor molecule within the pathway leading to aflatoxin production. Phylogenetic assessment, using ITS, BenA, CaM, and RBP2 gene sequences, reveals distinct clusters within Aspergillus sections and highlights the co-evolution of aflatoxigenic and non-aflatoxigenic species. Aspergillus ochraceoroseus and A. rambellii diverged out of aflatoxin-producing species earlier in evolutionary history, before splitting from a shared ancestor with A. fumigatus, which neither produces aflatoxins nor sterigmatocystin. Non-aflatoxigenic species like A. oryzae may evolve from aflatoxigenic species like A. flavus due to variations in evolutionary rates, telomere deletions, and mutations in aflatoxin biosynthesis genes. Comparative genomic analysis of AF, AF/ST and ST gene cluster shows that A. flavus has a larger aflatoxin gene cluster, while A. ochraceoroseus lacks the genes aflP and aflQ. Additionally, A. ochraceoroseus and A. rambellii possess a smaller genome, suggesting that genetic drift and deletions have refined their genomes for more efficient aflatoxin production.

Purpose: The prognostic role of neurotransmitters and their receptors in breast cancer (BC) has not been fully investigated. The aim of this study was to construct a survival model for the prognosis of BC patients based on neurotransmitter receptor-related genes (NRRGs).

Methods: BC-related differentially expressed genes (DEGs) were screened and intersected with NRRGs. GO, KEGG and PPI analyses were performed. Univariate Cox, Least Absolute Shrinkage and Selection Operator (LASSO) and multivariate Cox regression analyses were used to construct prognostic models for biomarker expression levels. The model was validated using an external validation set. The receiver operating characteristic curves (ROC) for diagnostic value prediction and clinicopathologic characteristic nomogram were constructed. qRT-PCR was used for further in vitro validation experiments.

Results: Forty-five overlapping genes were obtained by intersecting BC-related DEGs with 172 NRRGs. Univariate Cox, LASSO and multivariate Cox regression analyses were used to construct prognostic models for the expression levels of biomarkers including DLG3, SLC1A1, PSCA and PRKCZ. The feasibility of the model was validated by the GEO validation set. ROC curves were established for diagnostic value prediction. Patients in the high-risk group had a worse prognosis, higher TMB score, higher probability of gene mutation, and higher immune cell infiltration. RiskScore, M, N and Age were strongly correlated with survival. The mRNA expression levels of DLG3, PSCA and PRKCZ in the BC group were significantly higher than those in the control group.

Conclusion: Risk prediction model based on DLG3, SLC1A1, PSCA and PRKCZ, which are closely related to BC prognosis, was successfully constructed.

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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.

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.