Genes In Genome Research Articles

The role of IQCB1 in liver cancer: a bioinformatics analysis.

Liver hepatocellular carcinoma (LIHC) is a prevalent malignancy globally, exhibiting substantial incidence and mortality rates. Early diagnosis and prevention of metastasis are crucial for the benefit of patients with liver cancer. The present study aimed to elucidate the involvement of IQCB1 in liver cancer through the utilization of bioinformatics. The samples utilized in this study were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Initially, the TCGA-LIHC dataset was employed to examine the expression of IQCB1, and its validation was performed on the GSE25097 dataset. Subsequently, Kaplan-Meier (KM) analysis was conducted to evaluate the prognostic significance of IQCB1 in LIHC, and its correlation with clinical pathological features was also investigated. Furthermore, a protein-protein interaction (PPI) network consisting of 20 proteins associated with IQCB1 was constructed using data from the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were carried out. A risk model was formulated to assess the prognostic significance and its prognostic value was compared to that of IQCB1 in isolation. Furthermore, an examination was conducted to explore the correlation between IQCB1 and immune infiltration, along with the involvement of immunological checkpoints. A drug sensitivity assessment of IQCB1 was performed using the Genomics of Drug Sensitivity in Cancer (GDSC) database. Additionally, the Tumor Immune Single-cell Hub (TISCH) database was utilized to investigate the association between IQCB1 and the tumor microenvironment (TME). The expression of IQCB1 was observed to be significantly elevated in tumor samples. Furthermore, patients with high expression levels of IQCB1 demonstrated a poorer prognosis. Additionally, IQCB1 exhibited significant correlations with MKI67, hepatitis B virus (HBV), hepatitis C virus (HCV), and alpha-fetoprotein (AFP). GO and KEGG analyses revealed enrichment of multiple signaling pathways. Subsequently, an investigation was conducted to examine the association between IQCB1 and the activity of ten signaling pathways related to tumor development. A positive correlation was observed between IQCB1 expression and T-helper 2 (Th2) cells, whereas a negative correlation was observed between IQCB1 expression and Th17 cells. Furthermore, a positive association was found between IQCB1 and immune checkpoints, particularly with CD276. Analysis of single-cell data from the TISCH database revealed widespread expression of IQCB1 in the TME. Additionally, screening revealed that among 12 drugs related to IQCB1, a subset of 10 drugs demonstrated negative correlations, whereas two drugs exhibited positive correlations. IQCB1 has the potential to function as a diagnostic and prognostic molecular marker, and its association with immune infiltration and checkpoint mechanisms has been observed.

Molecular genotyping and subgenotyping of duck circovirus at duck farms in Thailand

Background and Aim: Ducks worldwide are infected with duck circovirus (DuCV), which causes feather abnormality, emaciation, and poor growth performance. DuCV is similar to other circoviruses that induce immunosuppression due to the occurrence of the bursae of Fabricius (BF) and spleen atrophies. In Thailand, retarded ducks with feather losses were submitted for disease investigation. The ducks presented low body weight gain, had small BF and spleens, and were consistent with duck-infected DuCV. Our study investigated the possibility of DuCV infection in duck flocks in Thailand. We also analyzed the genetic characteristics of the virus. Materials and Methods: BF and spleen samples were collected from affected meat and layer ducks from six farms thought to have been infected with DuCV. These tissues were then subjected to histopathological examination and molecular identification using conventional polymerase chain reaction and nucleotide sequencing. To identify DuCV, phylogenetic trees were generated using MEGA version X software. Samples of tissues or swabs were collected to determine whether coinfections with bacteria and viruses existed. Results: Phylogenetic analysis using the entire genome (1995–1996 bp) and cap gene (762 bp) revealed that the DuCV isolates circulating in Thailand belonged to DuCV genotype I, which was further subdivided into two sub-genotypes: sub-genotype I b and an unclassified sub-genotype based on reference sub-genotypes. Thai isolates have variations in 10 amino acid residues in the capsid protein. Ducks infected with Thai DuCV were also coinfected with Riemerella anatipestifer, Escherichia coli, Pasteurella multocida, duck viral enteritis, and duck Tembusu virus, which is consistent with previous DuCV infection studies. Conclusion: Six DuCVs from ducks who were previously found to have feather loss, were underweight, had growth retardation, and had poor body condition were identified in this study as belonging to genotype Ⅰ and constituting at least two sub-genotypes. Due to the immunosuppressive effects of DuCV, coinfection of bacterial and viral pathogens was typically observed in Thai DuCV-infected ducks. Keywords: duck, duck circovirus, genetic characterization, immunosuppression, phylogenetic tree.

Relics of interspecific hybridization retained in the genome of a drought-adapted peanut cultivar.

Peanut (Arachis hypogaea L.) is a globally important oil and food crop frequently grown in arid, semi-arid, or dryland environments. Improving drought tolerance is a key goal for peanut crop improvement efforts. Here we present the genome assembly and gene model annotation for 'Line8', a peanut genotype bred from drought tolerant cultivars. Our assembly and annotation are the most contiguous and complete peanut genome resources currently available. The high contiguity of the Line8 assembly allowed us to explore structural variation both between peanut genotypes and subgenomes. We detect several large inversions between Line8 and other peanut genome assemblies, and there is a trend for the inversions between more genetically diverged genotypes to have higher gene content. We also relate patterns of subgenome exchange to structural variation between Line8 homeologous chromosomes. Unexpectedly, we discover that Line8 harbors an introgression from A.cardenasii, a diploid peanut relative and important donor of disease resistance alleles to peanut breeding populations. The fully resolved sequences of both haplotypes in this introgression provide the first in situ characterization of A.cardenasii candidate alleles that can be leveraged for future targeted improvement efforts. The completeness of our genome will support peanut biotechnology and broader research into the evolution of hybridization and polyploidy.

Enriched G4 forming repeats in the human genome are associated with robust well-coordinated transcription and reduced cancer transcriptome variation

Non-B DNA G-quadruplex (G4) structures with guanine (G) runs of 2-4 repeats can trigger opposing experimental transcriptional impacts. Here, we employed bioinformatic algorithms to comprehensively assess correlations of steady-state RNA transcript levels with all putative G4 sequence (pG4) locations genome-wide in three mammalian genomes and in normal and tumor human tissues. The human pG4-containing gene set displays higher expression levels than the set without pG4, supporting and extending some prior observations. pG4 enrichment at transcription start sites (TSS) in human, but not chimpanzee and mouse genomes, suggests possible positive selection pressure for pG4 at human TSS, potentially driving genome rewiring and gene expression divergence between human and chimpanzee. Comprehensive bioinformatic analyses revealed lower pG4-containing gene set variability in humans and among different pG4 genes in tumors. As G4 stabilizers are under therapeutic consideration for cancer and pathogens, such distinctions between human normal and tumor G4s along with other species merit attention. Furthermore, in germline and cancer sequences, the most mutagenic pG4 mapped to regions promoting alternative DNA structures. Overall findings establish high pG4 at TSS as a human genome attribute statistically associated with robust well-coordinated transcription and reduced cancer transcriptome variation with implications for biology, model organisms, and medicine.

Construction and verification of an innovative immune-related and hallmark gene sets prognostic model for bladder cancer.

Bladder cancer (BC) is a life-threatening malignancy with high mortality rates. Current prognostic models are insufficient in accurately predicting clinical outcomes, impeding personalized treatment strategies. This study aimed to identify BC subtypes and prognostic gene sets by analyzing changes in immune and hallmark gene sets activity in tumor and adjacent non-tumor tissues to enhance patient outcomes. Utilizing data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), gene set variation analysis (GSVA) was applied to C7 immune-related and hallmark gene sets from the Molecular Signatures Database (MSigDB). The CancerSubtype R package was utilized for clustering these gene sets into three categories, from which 109 candidate sets were identified using Venn diagrams. A refined subset of seven gene sets was selected through least absolute shrinkage and selection operator (LASSO) regression for the construction of a risk model. Model validity was confirmed with receiver operating characteristic (ROC) and calibration curves, and a nomogram was constructed to integrate risk scores with clinical parameters. Finally, genes from the gene sets of the model were acquired and analyzed for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and protein-protein interactions (PPI) via plugin Molecular Complex Detection (MCODE) and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) in Cytoscape in both tumor and non-tumor tissues. Three BC subtypes were characterized by immunologic and hallmark gene sets, with subtype 1 patients showing worse survival. The prognostic model, based on seven gene sets, effectively stratified risk, with high-risk patients having significantly shorter survival. GO, KEGG, and PPI analyses indicated distinct influences of non-tumor and tumor tissues on the prognosis of BC patients. We constructed and validated a novel prognostic model for risk stratification in BC based on immunologic and hallmark genes sets, which presents a novel perspective on rational treatment approaches and accurate prognostic evaluations for BC by considering both tumor and adjacent non-tumor tissues. This highlights the importance of focusing on alterations in both tumor and adjacent non-tumor tissues, rather than solely on the tumor itself.

Investigation of the Mechanism of SEMA5A and Its Associated Autophagy-Related Genes in Gastric Cancer.

Semaphorin 5A (SEMA5A) and autophagy-related genes (ARGs) are pivotal in the pathogenesis of gastric cancer (GC). However, the potential regulatory role of SEMA5A in autophagy via its associated ARGs and the underlying molecular mechanisms remain unresolved. GC-related datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to identify differentially expressed genes (DEGs) between GC and control samples. The intersection of DEGs with ARGs produced candidate genes, which were further analyzed using Spearman correlation with SEMA5A to identify signature genes. Stratification of GC samples based on signature gene expression, followed by Kaplan-Meier survival analysis, identified key genes. Subsequent analyses, including gene set enrichment analysis (GSEA), immune infiltration, and immune checkpoint evaluation, were conducted on the key genes and SEMA5A. The mRNA expression level was quantified using real-time quantitative polymerase chain reaction (RT-qPCR). Ninety candidate genes were identified for Spearman correlation with SEMA5A, revealing TNFSF11, BMP6, ITPR1, and DLC1 with correlation coefficients exceeding 0.3. Survival analysis underscored DLC1 and BMP6 as key genes due to significant prognostic differences. GSEA implicated SEMA5A, BMP6, and DLC1 in the ECM receptor interaction pathway. Immune infiltration analysis indicated a negative correlation of SEMA5A and BMP6 with M1 macrophages, while DLC1 exhibited the strongest association with the immune checkpoint PDCD1LG2 (p < 0.05, cor = 0.43). The mRNA expression level of SEMA5A was significantly upregulated in AGS parental cells compared to GES-1 cells (p < 0.01), whereas DLC1 and BMP6 mRNA levels were markedly downregulated in AGS parental cells relative to GES-1 (p < 0.0001). ARGs BMP6 and DLC1, associated with SEMA5A, were identified, and their prognostic significance in GC was demonstrated. Additionally, their regulatory mechanisms were further elucidated through immune infiltration analysis and molecular network construction, providing a theoretical foundation for future research on the molecular mechanisms in patients with GC.

ADP-glucose pyrophosphorylase gene family in soybean and implications in drought stress tolerance.

ADP-glucose pyrophosphorylase (AGPase) is the key rate-limiting enzyme in starch biosynthesis pathway, and has been identified as a potential target for manipulation strategies aimed at improving crop yield and quality. To identify the AGPase gene family members in soybean, and explore the potential implications of GmAGPS2 in drought stress tolerance. Thegenome-wide identification and sequence analysis of soybean AGPase gene family was carried out by bioinformatics methods. The GmAGP gene expression was analyzed using transcriptome data and quantitative real-time PCR (qRT-PCR). Furthermore, transgenic yeast strains overexpressing GmAGPS2 were generated, and their growth was observed under drought stress. In this study, we searched for AGPase genes (GmAGP) in the soybean genome and identified a total of 14 GmAGP genes. The GmAGP proteins had a unique conserved NTP_transferase domain and were mainly located in the chloroplast and cytosol. Evolutionarily, theGmAGP proteins can be clustered into two distinct subgroups; within the same subgroup, they displayed a similar distribution pattern of conserved motifs. The GmAGP genes exhibited an uneven distribution on 10 chromosomes, and segmental duplication contributed to AGPase gene family expansion in soybean. The GmAGP genes presented different tissue expression pattern, in which GmAGPL6, GmAGPL9, and GmAGPL10 mainly exhibited tissue-specific expression pattern. The promoter of GmAGP genes had multiple cis-acting elements related to phytohormones and stress responses, and 8 GmAGP genes contained drought-responsive cis-acting elements. qRT‒PCR analysis demonstrated a significant upregulation expression of GmAGPL6, GmAGPL10, and GmAGPS2 in response to drought stress. Further functional analysis indicated that GmAGPS2 gene could improve yeast growth under drought stress conditions and enhance the drought tolerance of yeast. These results will contribute to further elucidation of the function of GmAGP genes, and offer important candidate genes for the genetic improvement of starch and yield-related traits and the breeding of high drought stress tolerance varieties in soybean.

Genome-wide investigation of the nuclear factor Y gene family in Ginger (Zingiber officinale Roscoe): evolution and expression profiling during development and abiotic stresses

BackgroundNuclear factor Y (NF-Y) plays a vital role in numerous biological processes as well as responses to biotic and abiotic stresses. However, its function in ginger (Zingiber officinale Roscoe), a significant medicinal and dietary vegetable, remains largely unexplored. Although the NF-Y family has been thoroughly identified in many plant species, and the function of individual NF-Y TFs has been characterized, there is a paucity of knowledge concerning this family in ginger.MethodsWe identified the largest number of NF-Y genes in the ginger genome using two BLASTP methods as part of our ginger genome research project. The conserved motifs of NF-Y proteins were analyzed through this process. To examine gene duplication events, we employed the Multiple Collinearity Scan toolkit (MCScanX). Syntenic relationships of NF-Y genes were mapped using the Dual Synteny Plotter software. Multiple sequence alignments were performed with MUSCLE under default parameters, and the resulting alignments were used to generate a maximum likelihood (ML) phylogenetic tree with the MEGA X program. RNA-seq analysis was conducted on collected samples, and statistical analyses were performed using Sigma Plot v14.0 (SYSTAT Software, USA).ResultsIn this study, the ginger genome was utilized to identify 36 NF-Y genes (10 ZoNF-YAs, 16 ZoNF-YBs, and 10 ZoNF-YCs), which were renamed based on their chromosomal distribution. Ten distinct motifs were identified within the ZoNF-Y genes, with certain unique motifs being vital for gene function. By analyzing their chromosomal location, gene structure, conserved protein motifs, and gene duplication events, we gained a deeper understanding of the evolutionary characteristics of these ZoNF-Y genes. Detailed analysis of ZoNF-Y gene expression patterns across various tissues, performed through RNA-seq and qRT-PCR, revealed their significant role in regulating ginger rhizome and flower growth and development. Additionally, we identified the ZoNF-Y family genes that responded to abiotic stresses.ConclusionThis study represents the first identification of the ZoNF-Y family in ginger. Our findings contribute to research on evolutionary characteristics and provide a better understanding of the molecular basis for development and abiotic stress response. Furthermore, it lays the foundation for further functional characterization of ZoNF-Y genes with an aim of ginger crop improvement.

Activation and inhibition of sirtuins: From bench to bedside.

The sirtuin family comprises seven NAD+-dependent enzymes which catalyze protein lysine deacylation and mono ADP-ribosylation. Sirtuins act as central regulators of genomic stability and gene expression and control key processes, including energetic metabolism, cell cycle, differentiation, apoptosis, and aging. As a result, all sirtuins play critical roles in cellular homeostasis and organism wellness, and their dysregulation has been linked to metabolic, cardiovascular, and neurological diseases. Furthermore, sirtuins have shown dichotomous roles in cancer, acting as context-dependent tumor suppressors or promoters. Given their central role in different cellular processes, sirtuins have attracted increasing research interest aimed at developing both activators and inhibitors. Indeed, sirtuin modulation may have therapeutic effects in many age-related diseases, including diabetes, cardiovascular and neurodegenerative disorders, and cancer. Moreover, isoform selective modulators may increase our knowledge of sirtuin biology and aid to develop better therapies. Through this review, we provide critical insights into sirtuin pharmacology and illustrate their enzymatic activities and biological functions. Furthermore, we outline the most relevant sirtuin modulators in terms of their modes of action, structure-activity relationships, pharmacological effects, and clinical applications.

GGT5 as a promising prognostic biomarker and its effects on tumor cell progression in gastric cancer.

Gastric cancer (GC) is a gastric malignant tumor with over 1 million new cases globally each year. There are many diagnostic methods for GC, but due to the hidden early symptoms of GC, early GC is easy to be missed and misdiagnosed, which affects the follow-up treatment of patients. The early and accurate diagnosis of GC is of great significance for the treatment and survival of GC patients. Our laboratory study found that gamma-glutamyl transferase (GGT) was highly expressed in GC patients, but the mechanism of GGT family genes in the occurrence and development of GC remained to be further studied. Therefore, this study aimed to explore the mechanism of GGT family functional gene GGT5 regulating the proliferation and migration of GC cells, and provide a possible new biomarker for the early diagnosis of GC. The value of serum GGT in GC patients was first statistically analyzed. Then, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were used to analyze the mRNA expression of GGT5 in GC, and its clinical relationship and function. Furthermore, expression of GGT5 was reduced by lentivirus RNA interference and verified by polymerase chain reaction (PCR), Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to detect cell proliferation after GGT5 knockdown. Scratch and Transwell assays were applied to observe cell migration after knockdown of GGT5. Finally, Western blot assays were observed to demonstrate PI3K/AKT-MAPK and MMPs expression levels after knockdown of GGT5. Serum GGT was expressed at a high level in GC patients. GGT5 was highly expressed in GC tissues, and was associated with poor prognosis and clinical stage of GC. GGT5 might be involved in the regulation of vascular development and angiogenesis, as well as in the mechanisms of cell motility and migration, and it was positively correlated with the PI3K/AKT pathway. The proliferation and migration capacity of GC cells was dampened by downregulation of GGT5. GGT5 mediated proliferation and migration of GC cells by directly targeting PI3K/AKT-MAPK-MMPs pathways. Low expression of GGT5 reduced proliferation and migration in GC cells by modulating the PI3K/AKT-MAPK-MMPs pathway, and GGT5 might be a new target for GC.

Highly contiguous genome assembly and gene annotation of the short-finned eel (Anguilla bicolor pacifica)

In East Asia, anguillid eels are commercially important. However, unlike other species, they have not been successfully cultivated throughout their lifecycle. Facing population decline due to overharvesting and environmental pressures, the industry is turning to alternatives, such as Anguilla bicolor pacifica (short-finned eel). However, genomic data for short-finned eels are unavailable. Here, we present in-depth whole-genome sequencing results for short-finned eel obtained using two sequencing platforms (PacBio Revio, and Illumina). In this study, we achieved a highly contiguous genome assembly of the short-finned eel, comprising 19 pseudochromosomes encompassing 99.76% of the 1.087 Gb genome sequence with an N50 of 16.88 and 61.07 Mb from contig and scaffold, respectively. Transcripts from four different tissues led to the annotation of 23,095 protein-coding genes in the eel genome, 98.66% of which were functionally annotated. This high-quality genome assembly, along with the annotation data, provides a foundation for future functional genomic studies of short-finned eels.

NUSAP1 promotes gastric cancer radioresistance by inhibiting ubiquitination of ANXA2 and is suppressed by miR-129-5p

BackgroundRadiotherapy is an important strategy for the treatment of advanced gastric cancer (GC), while the radioresistance limits its effectiveness. Nucleolar and spindle associated protein 1 (NUSAP1) was implicated in cancer progression and chemoresistance. However, the underlying mechanisms of NUSAP1 influencing GC radioresistance remain largely unknown.MethodsMeta-analysis was conducted to systematically evaluate the prognostic value of NUSAP1 in human cancers. Gene set enrichment analysis (GSEA) was conducted using The Cancer Genome Atlas (TCGA) and gene expression omnibus (GEO) datasets. MRNA and protein expressions were detected by qRT-PCR and western blot, respectively. The radiosensitivity of GC cells was observed by colony formation, flow cytometry, comet, immunofluorescence, and animal assays. Immunoprecipitation assay and mass spectrometry were utilized to identify protein associations. MiRNAs binding with NUSAP1 were determined by starbase prediction, luciferase reporter, and RNA immunoprecipitation (RIP) assays.ResultsNUSAP1 high expression predicted worse overall survival (OS) and disease-free survival (DFS) with no statistical heterogeneity through the meta-analysis. Downregulation of NUSAP1 significantly increased GC radiosensitivity by inhibiting colony formation, DNA damage repair, and promoting apoptosis following irradiation. Additionally, NUSAP1 silencing combined with radiation resulted in a synergistic anti-tumor effect in xenograft mouse model. Mechanistically, NUSAP1 interacted with ANXA2, protecting it against protein degradation via impeding its ubiquitination process. NUSAP1 was confirmed as a target of miR-129-5p and negatively regulated by it.ConclusionOur results suggested that NUSAP1 enhanced the radioresistance of GC cells. NUSAP1 could be a promising target to increase GC radiosensitivity.

The construction and experimental verification of a 6-LncRNA model based on Lactic acid metabolism in the tumor microenvironment of Wilms tumor

BackgroundLactic acid (LA) can promote the malignant progression of tumors through the crosstalk with the tumor microenvironment (TME). However, the function of long non-coding RNAs (lncRNAs) related to LA metabolism in Wilms tumor (WT) remains unclear. MethodsGene expression data and clinical data of WT patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Through the ESTIMATE algorithm and Pearson correlation analysis, lncRNAs related to tumor immunity and LA metabolism were screened. Subsequently, Cox regression analysis and Lasso Cox regression analysis were used to construct a model. Furthermore, candidate genes were identified and a competitive endogenous RNA (ceRNA) network was conducted to explore the specific mechanism of characteristic genes. Finally, based on the strong clinical relevance of UNC5B-AS1, its expression and function were experimentally verified. ResultsThe immune score and stromal score were found to be closely related to the prognosis of WT. Eventually, a prognostic model (TME-LA-LM) consisting of 6 lncRNAs was successfully identified. The model demonstrated favorable predictive ability and accuracy, with significant variation in immune infiltration and drug susceptibility observed between risk groups. Additionally, the study revealed the involvement of 2 candidate genes and 5 microRNAs (miRNAs) in the tumor’s development. Notably, UNC5B-AS1 was highly expressed and found to promote the proliferation and migration of tumor cells. ConclusionThis study, for the first time, elucidated the prognostic signatures of WT using lncRNAs related to TME and LA metabolism. The fundings of this research offer valuable insights for future studies on immunotherapy, personalized chemotherapy and mechanism research.

Inhibiting the expression of spindle appendix cooled coil protein 1 can suppress tumor cell growth and metastasis and is associated with cancer immune cells in esophageal squamous cell carcinoma.

Inhibiting the expression of spindle appendix cooled coil protein 1 (SPDL1) can slow down disease progression and is related to poor prognosis in patients with esophageal cancer. However, the specific roles and molecular mechanisms of SPDL1 in esophageal squamous cell carcinoma (ESCC) have not been explored yet. The current study aimed to investigate the expression levels of SPDL1 in ESCC via transcriptome analysis using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases. Moreover, the biological roles, molecular mechanisms, and protein networks involved in SPDL1 were identified using machine learning and bioinformatics. The cell counting kit-8 assay, EdU staining, and transwell assay were used to investigate the effects of inhibiting SPDL1 expression on ESCC cell proliferation, migration, and invasion. Finally, the correlation between the SPDL1 expression and cancer immune infiltrating cells was evaluated by analyzing data from the TCGA database. Results showed that SPDL1 was overexpressed in the ESCC tissues. The SPDL1 expression was related to age in patients with ESCC. The SPDL1 co-expressed genes included those involved in cell division, cell cycle, DNA repair and replication, cell aging, and other processes. The high-risk scores of SPDL1-related long non-coding RNAs were significantly correlated with overall survival and cancer progression in patients with ESCC (P < 0.05). Inhibiting the SPDL1 expression was effective in suppressing the proliferation, migration, and invasion of ESCC TE-1 cells (P < 0.05). The overexpression of SPDL1 was positively correlated with the levels of Th2 and T-helper cells, and was negatively correlated with the levels of plasmacytoid dendritic cells and mast cells. In conclusion, SPDL1 was overexpressed in ESCC and was associated with immune cells. Further, inhibiting the SPDL1 expression could effectively slow down cancer cell growth and migration. SPDL1 is a promising biomarker for treating patients with ESCC.

Contribution of homoeologous exchange to domestication of polyploid Brassica

BackgroundPolyploidy is widely recognized as a significant evolutionary force in the plant kingdom, contributing to the diversification of plants. One of the notable features of allopolyploidy is the occurrence of homoeologous exchange (HE) events between the subgenomes, causing changes in genomic composition, gene expression, and phenotypic variations. However, the role of HE in plant adaptation and domestication remains unclear.ResultsHere we analyze the whole-genome resequencing data from Brassica napus accessions representing the different morphotypes and ecotypes, to investigate the role of HE in domestication. Our findings demonstrate frequent occurrence of HEs in Brassica napus, with substantial HE patterns shared across populations, indicating their potential role in promoting crop domestication. HE events are asymmetric, with the A genome more frequently replacing C genome segments. These events show a preference for specific genomic regions and vary among populations. We also identify candidate genes in HE regions specific to certain populations, which likely contribute to flowering-time diversification across diverse morphotypes and ecotypes. In addition, we assemble a new genome of a swede accession, confirming the HE signals on the genome and their potential involvement in root tuber development. By analyzing HE in another allopolyploid species, Brassica juncea, we characterize a potential broader role of HE in allopolyploid crop domestication.ConclusionsOur results provide novel insights into the domestication of polyploid Brassica species and highlight homoeologous exchange as a crucial mechanism for generating variations that are selected for crop improvement in polyploid species.

Heterochromatin formation and remodeling by IRTKS condensates counteract cellular senescence

Heterochromatin, a key component of the eukaryotic nucleus, is fundamental to the regulation of genome stability, gene expression and cellular functions. However, the factors and mechanisms involved in heterochromatin formation and maintenance still remain largely unknown. Here, we show that insulin receptor tyrosine kinase substrate (IRTKS), an I-BAR domain protein, is indispensable for constitutive heterochromatin formation via liquid‒liquid phase separation (LLPS). In particular, IRTKS droplets can infiltrate heterochromatin condensates composed of HP1α and diverse DNA-bound nucleosomes. IRTKS can stabilize HP1α by recruiting the E2 ligase Ubc9 to SUMOylate HP1α, which enables it to form larger phase-separated droplets than unmodified HP1α. Furthermore, IRTKS deficiency leads to loss of heterochromatin, resulting in genome-wide changes in chromatin accessibility and aberrant transcription of repetitive DNA elements. This leads to activation of cGAS-STING pathway and type-I interferon (IFN-I) signaling, as well as to the induction of cellular senescence and senescence-associated secretory phenotype (SASP) responses. Collectively, our findings establish a mechanism by which IRTKS condensates consolidate constitutive heterochromatin, revealing an unexpected role of IRTKS as an epigenetic mediator of cellular senescence.

A novel model based on lipid metabolism-related genes associated with immune microenvironment predicts metastasis of breast cancer

BackgroundBreast cancer (BC) is the most prevalent malignant tumor among women worldwide and a significant cause of cancer-related deaths in females. Recent studies have shown that lipid metabolism-related genes (LMRGs) exhibit prognostic potential in various types of tumors, including BC. Our study aimed to establish a novel model to predict the metastasis of BC.MethodsClinical information and corresponding RNA data of patients with BC were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. Consensus clustering was performed to identify novel molecular subgroups. Estimation of Stromal and Immune Cells in Malignant Tumor Tissues using Expression, microenvironment cell populations counter, microenvironment cell populations counter, and single-sample gene set enrichment analyses were employed to determine the tumor immune microenvironment and immune status of the identified subgroups. Functional analyses, including Gene Ontology and gene set enrichment analyses, were conducted to elucidate the underlying mechanisms. A prognostic risk model was constructed using the Least Absolute Shrinkage and Selection Operator algorithm and multivariate Cox regression analysis.ResultsThis study identified differential gene expression between patients with BC exhibiting metastasis and those without metastasis using public databases. Using the obtained data, we established predictive models based on six LMRGs. Furthermore, consensus clustering and prognostic score grouping analysis revealed that differentially expressed LMRGs influence tumor prognosis by regulating tumor immunity. To facilitate clinical application, we developed a nomogram integrating the risk model and clinical characteristics to accurately predict the prognosis of patients with BC.ConclusionWe developed and validated a novel signature associated with LMRGs for predicting disease-free survival in patients with BC. The expression of LMRGs correlates with the immune microenvironment of patients with BC, providing new insights and improved strategies for the diagnosis and treatment of BC.

Genome‐wide association analysis of resistance to anthracnose in the Middle American Diversity Panel of common bean (Phaseolus vulgaris L.)

AbstractAnthracnose (ANTH) caused by Colletotrichum lindemuthianum is a major disease of common bean (Phaseolus vulgaris L.). The genetic basis of ANTH resistance in the Middle American Diversity Panel (MDP) is unknown. The objectives of this study were to identify (1) Middle American accessions resistant to races 7, 19, 51, 63, 167, and 1085 of C. lindemuthianum and (ii) genomic regions and positional candidate genes associated with resistance to these races. The MDP composed of 240 Middle American accessions was evaluated for resistance to races 7, 19, 51, 63, 167, and 1085. The MDP was genotyped with 211,763 single nucleotide polymorphisms (SNPs), and mixed linear model analysis was conducted to identify genomic regions associated with resistance to the six races. Seven accessions were highly resistant to all six races, and these can be used as sources of resistance to improve specific market classes in the Middle American gene pool. The genomic region (385,894 bp) on chromosome Pv04 was significantly associated with resistance to race 167. Genomic regions on Pv02 (41,570,325 bp), Pv07 (24,122,343 bp), and Pv11 (51,707,917 bp) were significantly associated with resistance to race 19. Disease resistance (R) genes with the nucleotide binding‐APAF resistance protein and CED‐4 domain were identified as positional candidate genes on Pv04 and Pv11. There were no SNPs significantly associated with resistance to races 7, 51, 63, and 1085. Pyramiding the identified genomic regions on Pv04, Pv07, and Pv11 could provide durable ANTH resistance in Middle American varieties for races 19 and 167.

Establish TIIC signature score based the machine learning fusion in bladder cancer

BackgroundBladder cancer is a prevalent malignant tumor with high heterogeneity. Current treatments, such as transurethral resection of bladder tumor (TURBT) and intravesical Bacillus Calmette-Guérin (BCG) therapy, still have limitations, with approximately 30% of non-muscle-invasive bladder cancer (NMIBC) progressing to muscle-invasive bladder cancer (MIBC), and a substantial number of MIBC patients experiencing recurrence after surgery. Immunotherapy has shown potential benefits, but accurate prediction of its prognostic effects remains challenging.MethodsWe analyzed bladder cancer RNA-seq data and clinical information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and used various machine learning algorithms to screen for feature RNAs related to tumor-infiltrating immune cells (TIICs) from single-cell data. Based on these RNAs, we established a TIIC signature score and evaluated its relationship with overall survival (OS) and immunotherapy response in bladder cancer patients.ResultsThe study identified 171 TIIC-RNAs and selected 11 TIIC-RNAs with prognostic value through survival analysis. The TIIC signature score established using a machine learning fusion method was significantly associated with OS and showed good predictive performance in different datasets. Additionally, the signature score was negatively correlated with immunotherapy response, with patients with low TIIC feature scores showing better survival outcomes after immunotherapy. Further biological functional analysis revealed a close association between the TIIC signature score and immune regulation processes, cellular metabolism, and genetic variations.ConclusionThis study successfully constructed and validated an RNA signature scoring system based on tumor-infiltrating immune cell (TIIC) features, which can effectively predict OS and the effectiveness of immunotherapy in bladder cancer patients.

Comprehensive exploration on the role of base excision repair genes in modulating immune infiltration in low-grade glioma

IntroductionGlioma is a brain tumour occurring in all age groups but common in adults. Despite advances in the understanding of tumours, we cannot improve the survival of the patients and do not have an appropriate biomarker for progression and prognosis prediction. The base excision repair mechanism maintains the integrity of the genome, preventing tumour formation. However, continuous chemical damage to the cells results in mutations that escape the repair mechanism and support tumour growth. The tumour microenvironment in cancer is crucial in determining the tumour growth, development, and response to treatments. The present study explored the significance of Base Excision Repair genes (BER) in modulating the tumour microenvironment. MethodsWe used the publically available data sets from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to explore the role of the base excision repair gene in the modulating tumour microenvironment. The data was analysed for the expression of base excision repair genes, their correlation with the immune markers, their prognostic potential, and enrichment analysis to understand the pathways they modulate in low-grade glioma (LGG) progression. ResultsThe analysis showed BER genes contribute an integral role in the overall and disease-free survival of LGG. Genes like MUTYH, PNKP, UNG and XRCC1 showed a correlation with the immune infiltration levels and a significant correlation with various immune markers associated with different immune cells, including tumour-associated macrophages. MUTYH, UNG and XRCC1 correlated with IDH1 mutation status, and functional enrichment analysis showed that these genes are enriched in several pathways like Wnt, PD-1 and Integrin signalling. ConclusionOur findings suggest that the BER genes MUTYH, PNKP, UNG and XRCC1 can potentially be prognostic biomarkers and highly correlate with the immune cells of the tumour microenvironment.