Plant peroxidase (POD) belongs to multigene family, which not is only one of the important enzymes responsible for the removal of active oxygen radicals, but also participates in a variety of physiological and bioch...Plant peroxidase (POD) belongs to multigene family, which not is only one of the important enzymes responsible for the removal of active oxygen radicals, but also participates in a variety of physiological and biochemical processes and plays a crucial role in the maintenance of plant growth and development. In this study, the structures and functions of proteins encoded by 73 gene of POD family in Arabidopsis were analyzed with bioinformatics method, including the number of amino acids, isoelectric point, transmemberane domains, signal peptides, secondary structures and phosphorylation sites, and the phylogenic trees with and without signal peptides were constructed by using Mega4.0 software, to investigate the structural characteristics. In addition, the structures of AtPER members were analyzed, to reveal the relationship between the structures and functions, thereby providing theoretical basis for the research of plant oxidative stress resistance.展开更多
Arabidopsis thaliana ovate family proteins (AtOFPs) is a newly found plant-specific protein family interacting with TALE (3-aa loop extension homeodomain proteins) homeodomain proteins in Arabidopsis. Here, based ...Arabidopsis thaliana ovate family proteins (AtOFPs) is a newly found plant-specific protein family interacting with TALE (3-aa loop extension homeodomain proteins) homeodomain proteins in Arabidopsis. Here, based on bioinformatic analysis, we found that Arabidopsis genome actually encoded 17 OVATE domain-containing proteins. One of them, AtOFP19, has not been previously identified. Based on their amino acid sequence similarity, AtOFPs proteins can be divided into two groups. Most of the AtOFPs were located in nuclear, four of them were presented in chloroplast and the remaining two members appeared in cytoplasmic. A genome- wide microarray based gene expression analysis involving 47 stages of vegetative and reproductive development revealed that AtOFPs have diverse expression pattems. Investigation of proteins interaction showed that nine AtOFPs only interacted with TALE homeodomain proteins, which are fundamental regulators of plant meristem function and leaf development. Our work could provide important leads toward functional genomics studies of ovate family proteins, which may be involved in a previously unrecognized control mechanism in plant development展开更多
Previous studies have shown that Arabidopsis equilibrative nucleoside transporters (AtENTs) possess transport activities when produced in yeast cells and are differentially expressed in Arabidopsis organs. Herein, w...Previous studies have shown that Arabidopsis equilibrative nucleoside transporters (AtENTs) possess transport activities when produced in yeast cells and are differentially expressed in Arabidopsis organs. Herein, we report further analysis on the nucleoside transport activities and transcriptional patterns of AtENT members. The recombinant proteins of AtENTs 3, 6, and 7, but not those of AtENTs 1, 2, 4, and 8, were found to transport thymidine with high affinity. Contrary to previ- ous suggestion that AtENT 1 may not transport uridine, this work showed that recombinant AtENT 1 was a pH-dependent and high-affinity transporter of uridine. When grown on MS plates, the AtENT3 knockout plants were more tolerant to the cytotoxic uridine analog 5-fluorouridine than wild-type plants and the knockout plants ofAtENT 1 or AtENT6. Con- sistent with this observation, the AtENT3 knockout line exhibited a significantly decreased ability to take up [^3H]uridine via the roots when compared with wild-type plants and the plants with mutated AtENT 1 or AtENT6. This indicates that AtENT3, but not AtENTs 1 and 6, is the main transporter for uridine uptake in Arabidopsis roots. The transcription of AtENTs 1, 3, 4, 6, 7, and 8 was regulated in a complex manner during leaf development and senescence. In contrast, the six AtENT members were coordinately induced during seed germination. This work provides new information on the transport properties of recombinant AtENT proteins and new clues for future studies of the in vivo transport activities and physiological functions of the different ENT proteins in Arabidopsis plants.展开更多
The enzyme myo-inositol-1-phosphate synthase(MIPS EC 5.5.1.4) catalyzes the first step of myo-inositol biosynthesis, a product that plays crucial roles in plants as an osmoprotectant, transduction molecule, cell wal...The enzyme myo-inositol-1-phosphate synthase(MIPS EC 5.5.1.4) catalyzes the first step of myo-inositol biosynthesis, a product that plays crucial roles in plants as an osmoprotectant, transduction molecule, cell wall constituent and production of stress related molecule. Previous reports highlighted an important role of MIPS family genes in abiotic stresses particularly under salt stress tolerance in several plant species; however, little is known about the cellular and physiological functions of MIPS2 genes under abiotic conditions. In this study, a novel salt stress responsive gene designated Gs MIPS2 from wild soybean Glycine soja 07256 was functionally characterized contained an open reading frame(ORF) of 1 533 bp coding a peptide sequence of 510 amino acids along with mass of 56 445 ku. Multiple sequence alignment analysis revealed its 92%-99% similarity with other MIPS family members in legume proteins. Quantitative real-time PCR results demonstrated that Gs MIPS2 was induced by salt stress and expressed in roots of soybean. The positive function of Gs MIPS2 under salt response at different growth stages of transgenic Arabidopsis was also elucidated. The results showed that Gs MIPS2 transgenic lines displayed increased tolerance as compared to WT and atmips2 mutant lines under salt stress. Furthermore, the expression levels of some salt stress responsive marker genes, including KIN1, RD29 A, RD29 B, P5 Cs and COR47 were significantly up-regulated in Gs MIPS2 overexpression lines than wild type and atmips2 mutant. Collectively, these results suggested that Gs MIPS2 gene was a positive regulator of plant tolerance to salt stress. This was the first report to demonstrate that overexpression of Gs MIPS2 gene from wild soybean improved salt tolerance in transgenic Arabidopsis.展开更多
[Objective] The study was to analyze the structure and function of HpaGXoo and the relationship between the two.[Method] Some related bioinformatics analysis software on internet such as NPSA,Swiss-Model,SAPS and Inte...[Objective] The study was to analyze the structure and function of HpaGXoo and the relationship between the two.[Method] Some related bioinformatics analysis software on internet such as NPSA,Swiss-Model,SAPS and InterPro Scan were adopted to analyze the structure and predict its function.[Result] HpaGXoo consists of 139 amino acids,and has many alpha-helical and coiled structure,no signal peptide on N-terminal and no transmembrane structure.It locates in bacterial cytoplasm.[Conclusion] The study will lay ...展开更多
AIM To identify multiple micro RNAs(mi RNAs) for predicting the prognosis of gastric cancer(GC) patients by bioinformatics analysis.METHODS The original microarray dataset GSE93415,which included 20 GC and 20 tumor ad...AIM To identify multiple micro RNAs(mi RNAs) for predicting the prognosis of gastric cancer(GC) patients by bioinformatics analysis.METHODS The original microarray dataset GSE93415,which included 20 GC and 20 tumor adjacent normal gastric mucosal tissues,was downloaded from the Gene Expression Omnibus database and used for screening differentially expressed mi RNAs(DEMs).The cutoff criteria were P < 0.05 and fold change > 2.0.In addition,we acquired the mi RNA expression profiles and clinical information of 361 GC patients from The Cancer Genome Atlas database to assess the prognostic role of the DEMs.The target genes of mi RNAs were predicted using Target Scan,mi RDB,mi RWalk,and DIANA,and then the common target genes were selected for functional enrichment analysis.RESULTS A total of 110 DEMs including 19 up-regulated and 91 down-regulated mi RNAs were identified between 20 pairs of GC and tumor adjacent normal tissues,and the Kaplan-Meier survival analysis found that a threemi RNA signature(mi R-145-3 p,mi R-125 b-5 p,and mi R-99 a-5 p) had an obvious correlation with the survival of GC patients.Furthermore,univariate and multivariate Cox regression analyses indicated that the three-mi RNA signature could be a significant prognostic marker in GC patients.The common target genes of the three mi RNAs are added up to 108 and used for Gene Functional Enrichment analysis.Biological Process and Molecular Function analyses showed that the target genes are involved in cell recognition,gene silencing and nucleic acid binding,transcription factor activity,and transmembrane receptor activity.Cellular Component analysis revealed that the genes are portion of nucleus,chromatin silencing complex,and TORC1/2 complex.Biological Pathway analysis indicated that the genes participate in several cancer-related pathways,such as the focal adhesion,PI3 K,and m TOR signaling pathways.CONCLUSION This study justified that a three-mi RNA signature could play a role in predicting the survival of GC patients.展开更多
Pre‐harvest sprouting(PHS) seriously affects wheat yield and quality of the grain. ABI3 is a key factor in the activation of seed development and repression of germination in Arabidopsis. An ABI3‐interacting prot...Pre‐harvest sprouting(PHS) seriously affects wheat yield and quality of the grain. ABI3 is a key factor in the activation of seed development and repression of germination in Arabidopsis. An ABI3‐interacting protein(AIP2) could polyubiquitinate ABI3, impair seed dormancy and promote seed germination in Arabidopsis. In this study,two wheat AIP2 genes, TaAIP2A and TaAIP2B, were isolated.Subcellular localization assay and yeast two‐hybrid analysis revealed that TaAIP2A and TaAIP2B may function through interaction with wheat Viviporous‐1(TaVp1). The transcripts TaAIP2A and TaAIP2B were more abundant in wheat PHS susceptible cultivars than that of resistant ones, and decreased gradually following seed development. Expression of TaAIP2A and TaAIP2B in Arabidopsis aip2‐1 mutant lines resulted in earlier flowering, promotion of seed germination,and reduced ABA sensitivity, respectively, somehow mimicking the phenotype of the wild type, with TaAIP2B having a stronger role in these aspects. Furthermore, the expression ofupstream genes ABI1 and ABI2 were upregulated, whereas that of downstream genes ABI3 and ABI5 were downregulated in both TaAIP2A and TaAIP2B complemented lines upon ABA treatment. These results suggested that wheat AIP2s could negatively regulate the ABA signaling pathway and play important roles in seed germination, and thus wheat PHS resistance finally.展开更多
Computational methods have significantly transformed biomedical research,offering a comprehensive exploration of disease mechanisms and molecular protein functions.This article reviews a spectrum of computational tools...Computational methods have significantly transformed biomedical research,offering a comprehensive exploration of disease mechanisms and molecular protein functions.This article reviews a spectrum of computational tools and network analysis databases that play a crucial role in identifying potential interactions and signaling networks contributing to the onset of disease states.The utilization of protein/gene interaction and genetic variation databases,coupled with pathway analysis can facilitate the identification of potential drug targets.By bridging the gap between molecular-level information and disease understanding,this review contributes insights into the impactful utilization of computational methods,paving the way for targeted interventions and therapeutic advancements in biomedical research.展开更多
BACKGROUND Heart failure is a health burden responsible for high morbidity and mortality worldwide, and dilated cardiomyopathy(DCM) is one of the most common causes of heart failure. DCM is a disease of the heart musc...BACKGROUND Heart failure is a health burden responsible for high morbidity and mortality worldwide, and dilated cardiomyopathy(DCM) is one of the most common causes of heart failure. DCM is a disease of the heart muscle and is characterized by enlargement and dilation of at least one ventricle alongside impaired contractility with left ventricular ejection fraction < 40%. It is also associated with abnormalities in cytoskeletal proteins, mitochondrial ATP transporter, microvasculature, and fibrosis. However, the pathogenesis and potential biomarkers of DCM remain to be investigated.AIM To investigate the candidate genes and pathways involved in DCM patients.METHODS Two expression datasets(GSE3585 and GSE5406) were downloaded from the Gene Expression Omnibus database. The differentially expressed genes(DEGs) between the DCM patients and healthy individuals were identified using the R package “linear models for microarray data.” The pathways with common DEGs were analyzed via Gene Ontology(GO), Kyoto Encyclopedia of Genes and Genomes(KEGG), and gene set enrichment analyses. Moreover, a protein-protein interaction network(PPI) was constructed to identify the hub genes and modules. The MicroRNA Database was applied to predict the microRNAs(miRNAs) targeting the hub genes. Additionally, immune cell infiltration in DCM was analyzed using CIBERSORT.RESULTS In total, 97 DEGs(47 upregulated and 50 downregulated) were identified. GO analysis showed that the DEGs were mainly enriched in “response to growth factor,” “extracellular matrix,” and “extracellular matrix structural constituent.” KEGG pathway analysis indicated that the DEGs were mainly enriched in “protein digestion and absorption” and “interleukin 17(IL-17) signaling pathway.” The PPI network suggested that collagen type Ⅲ alpha 1 chain(COL3A1) and COL1A2 contribute to the pathogenesis of DCM. Additionally, visualization of the interactions between miRNAs and the hub genes revealed that hsa-miR-5682 and hsa-miR-4500 interacted with both COL3A1 and COL1A2, and thus these miRNAs might play roles in DCM. Immune cell infiltration analysis revealed that DCM patients had more infiltrated plasma cells and fewer infiltrated B memory cells, T follicular helper cells, and resting dendritic cells.CONCLUSION COL1A2 and COL3A1 and their targeting miRNAs, hsa-miR-5682 and hsa-miR-4500, may play critical roles in the pathogenesis of DCM, which are closely related to the IL-17 signaling pathway and acute inflammatory response. These results may provide useful clues for the diagnosis and treatment of DCM.展开更多
乳腺癌脑转移(breast cancer brain metastasis,BCBM)的发病机制尚未明确。为了探究BCBM的发病机制,对BCBM差异表达基因的生物学功能进行研究并筛选关键调控基因。从基因表达综合数据库(gene expression omnibus,GEO)下载4个BCBM基因表...乳腺癌脑转移(breast cancer brain metastasis,BCBM)的发病机制尚未明确。为了探究BCBM的发病机制,对BCBM差异表达基因的生物学功能进行研究并筛选关键调控基因。从基因表达综合数据库(gene expression omnibus,GEO)下载4个BCBM基因表达谱数据(GSE12237、GSE100534、GSE125989以及GSE43837),采用R语言筛选差异表达基因,采用富集分析包括基因本体分析(gene ontology,GO)和京都基因与基因组百科全书分析(Kyoto encyclopedia of genes and genomes,KEGG)进行生物学功能分析,采用STRING和Cytoscape分析蛋白质相互作用网络,采用Kaplan-Meier进行生存分析。结果表明,同时存在于2个及以上基因表达谱数据中的差异表达基因261个,GO分析主要涉及细胞外基质组织、细胞外结构组织等生物过程,细胞外基质结构组成、胶原结合等分子功能,含有胶原的细胞外基质、胶原蛋白三聚物等细胞组分;KEGG分析主要涉及蛋白质消化和吸收、局部黏附等通路。蛋白质相互作用网络分析得到9个关键调控基因,其中,DCN、COL6A1与BCBM的生存率显著相关,可作为潜在的BCBM关键调控基因,并为BCBM分子机制的研究提供思路。展开更多
基金Supported by National Natural Science Foundation of China(31070361)the Fundamental Research Funds for the Central Universities(0910KYZY43,1112KYQN31)+1 种基金"985 Project"from Minzu University of China(MUC98504-14)Scientific Research Project from State Ethnic Affairs Commission(10ZY01)~~
文摘Plant peroxidase (POD) belongs to multigene family, which not is only one of the important enzymes responsible for the removal of active oxygen radicals, but also participates in a variety of physiological and biochemical processes and plays a crucial role in the maintenance of plant growth and development. In this study, the structures and functions of proteins encoded by 73 gene of POD family in Arabidopsis were analyzed with bioinformatics method, including the number of amino acids, isoelectric point, transmemberane domains, signal peptides, secondary structures and phosphorylation sites, and the phylogenic trees with and without signal peptides were constructed by using Mega4.0 software, to investigate the structural characteristics. In addition, the structures of AtPER members were analyzed, to reveal the relationship between the structures and functions, thereby providing theoretical basis for the research of plant oxidative stress resistance.
基金Supported by the National Natural Science Foundation of China (30870144)
文摘Arabidopsis thaliana ovate family proteins (AtOFPs) is a newly found plant-specific protein family interacting with TALE (3-aa loop extension homeodomain proteins) homeodomain proteins in Arabidopsis. Here, based on bioinformatic analysis, we found that Arabidopsis genome actually encoded 17 OVATE domain-containing proteins. One of them, AtOFP19, has not been previously identified. Based on their amino acid sequence similarity, AtOFPs proteins can be divided into two groups. Most of the AtOFPs were located in nuclear, four of them were presented in chloroplast and the remaining two members appeared in cytoplasmic. A genome- wide microarray based gene expression analysis involving 47 stages of vegetative and reproductive development revealed that AtOFPs have diverse expression pattems. Investigation of proteins interaction showed that nine AtOFPs only interacted with TALE homeodomain proteins, which are fundamental regulators of plant meristem function and leaf development. Our work could provide important leads toward functional genomics studies of ovate family proteins, which may be involved in a previously unrecognized control mechanism in plant development
基金This work was supported by grants from the National Natural Science Foundation of China (39770491) the Chinese Academy of Sciences (KSCX2-SW-304).
文摘Previous studies have shown that Arabidopsis equilibrative nucleoside transporters (AtENTs) possess transport activities when produced in yeast cells and are differentially expressed in Arabidopsis organs. Herein, we report further analysis on the nucleoside transport activities and transcriptional patterns of AtENT members. The recombinant proteins of AtENTs 3, 6, and 7, but not those of AtENTs 1, 2, 4, and 8, were found to transport thymidine with high affinity. Contrary to previ- ous suggestion that AtENT 1 may not transport uridine, this work showed that recombinant AtENT 1 was a pH-dependent and high-affinity transporter of uridine. When grown on MS plates, the AtENT3 knockout plants were more tolerant to the cytotoxic uridine analog 5-fluorouridine than wild-type plants and the knockout plants ofAtENT 1 or AtENT6. Con- sistent with this observation, the AtENT3 knockout line exhibited a significantly decreased ability to take up [^3H]uridine via the roots when compared with wild-type plants and the plants with mutated AtENT 1 or AtENT6. This indicates that AtENT3, but not AtENTs 1 and 6, is the main transporter for uridine uptake in Arabidopsis roots. The transcription of AtENTs 1, 3, 4, 6, 7, and 8 was regulated in a complex manner during leaf development and senescence. In contrast, the six AtENT members were coordinately induced during seed germination. This work provides new information on the transport properties of recombinant AtENT proteins and new clues for future studies of the in vivo transport activities and physiological functions of the different ENT proteins in Arabidopsis plants.
基金Supported by "863" Project(2008AA10Z153)the National Natural Science Foundation of China(31171578)+1 种基金Heilongjiang Provincial Higher School Science and Technology Innovation Team Building Program(2011TD005)the National Basic Scientific Talent Training Fund Projects(J1210069)
文摘The enzyme myo-inositol-1-phosphate synthase(MIPS EC 5.5.1.4) catalyzes the first step of myo-inositol biosynthesis, a product that plays crucial roles in plants as an osmoprotectant, transduction molecule, cell wall constituent and production of stress related molecule. Previous reports highlighted an important role of MIPS family genes in abiotic stresses particularly under salt stress tolerance in several plant species; however, little is known about the cellular and physiological functions of MIPS2 genes under abiotic conditions. In this study, a novel salt stress responsive gene designated Gs MIPS2 from wild soybean Glycine soja 07256 was functionally characterized contained an open reading frame(ORF) of 1 533 bp coding a peptide sequence of 510 amino acids along with mass of 56 445 ku. Multiple sequence alignment analysis revealed its 92%-99% similarity with other MIPS family members in legume proteins. Quantitative real-time PCR results demonstrated that Gs MIPS2 was induced by salt stress and expressed in roots of soybean. The positive function of Gs MIPS2 under salt response at different growth stages of transgenic Arabidopsis was also elucidated. The results showed that Gs MIPS2 transgenic lines displayed increased tolerance as compared to WT and atmips2 mutant lines under salt stress. Furthermore, the expression levels of some salt stress responsive marker genes, including KIN1, RD29 A, RD29 B, P5 Cs and COR47 were significantly up-regulated in Gs MIPS2 overexpression lines than wild type and atmips2 mutant. Collectively, these results suggested that Gs MIPS2 gene was a positive regulator of plant tolerance to salt stress. This was the first report to demonstrate that overexpression of Gs MIPS2 gene from wild soybean improved salt tolerance in transgenic Arabidopsis.
基金Supported by Langfang Teachers College Research Grant(LSZB200803)~~
文摘[Objective] The study was to analyze the structure and function of HpaGXoo and the relationship between the two.[Method] Some related bioinformatics analysis software on internet such as NPSA,Swiss-Model,SAPS and InterPro Scan were adopted to analyze the structure and predict its function.[Result] HpaGXoo consists of 139 amino acids,and has many alpha-helical and coiled structure,no signal peptide on N-terminal and no transmembrane structure.It locates in bacterial cytoplasm.[Conclusion] The study will lay ...
基金Supported by National Natural Science Foundation of China,No.30572162Natural Science Foundation of Liaoning Province,No.201602817
文摘AIM To identify multiple micro RNAs(mi RNAs) for predicting the prognosis of gastric cancer(GC) patients by bioinformatics analysis.METHODS The original microarray dataset GSE93415,which included 20 GC and 20 tumor adjacent normal gastric mucosal tissues,was downloaded from the Gene Expression Omnibus database and used for screening differentially expressed mi RNAs(DEMs).The cutoff criteria were P < 0.05 and fold change > 2.0.In addition,we acquired the mi RNA expression profiles and clinical information of 361 GC patients from The Cancer Genome Atlas database to assess the prognostic role of the DEMs.The target genes of mi RNAs were predicted using Target Scan,mi RDB,mi RWalk,and DIANA,and then the common target genes were selected for functional enrichment analysis.RESULTS A total of 110 DEMs including 19 up-regulated and 91 down-regulated mi RNAs were identified between 20 pairs of GC and tumor adjacent normal tissues,and the Kaplan-Meier survival analysis found that a threemi RNA signature(mi R-145-3 p,mi R-125 b-5 p,and mi R-99 a-5 p) had an obvious correlation with the survival of GC patients.Furthermore,univariate and multivariate Cox regression analyses indicated that the three-mi RNA signature could be a significant prognostic marker in GC patients.The common target genes of the three mi RNAs are added up to 108 and used for Gene Functional Enrichment analysis.Biological Process and Molecular Function analyses showed that the target genes are involved in cell recognition,gene silencing and nucleic acid binding,transcription factor activity,and transmembrane receptor activity.Cellular Component analysis revealed that the genes are portion of nucleus,chromatin silencing complex,and TORC1/2 complex.Biological Pathway analysis indicated that the genes participate in several cancer-related pathways,such as the focal adhesion,PI3 K,and m TOR signaling pathways.CONCLUSION This study justified that a three-mi RNA signature could play a role in predicting the survival of GC patients.
基金partly funded by the China National Basic Research Program supported by the Chinese Ministry of Science and Technology(2009CB118300)
文摘Pre‐harvest sprouting(PHS) seriously affects wheat yield and quality of the grain. ABI3 is a key factor in the activation of seed development and repression of germination in Arabidopsis. An ABI3‐interacting protein(AIP2) could polyubiquitinate ABI3, impair seed dormancy and promote seed germination in Arabidopsis. In this study,two wheat AIP2 genes, TaAIP2A and TaAIP2B, were isolated.Subcellular localization assay and yeast two‐hybrid analysis revealed that TaAIP2A and TaAIP2B may function through interaction with wheat Viviporous‐1(TaVp1). The transcripts TaAIP2A and TaAIP2B were more abundant in wheat PHS susceptible cultivars than that of resistant ones, and decreased gradually following seed development. Expression of TaAIP2A and TaAIP2B in Arabidopsis aip2‐1 mutant lines resulted in earlier flowering, promotion of seed germination,and reduced ABA sensitivity, respectively, somehow mimicking the phenotype of the wild type, with TaAIP2B having a stronger role in these aspects. Furthermore, the expression ofupstream genes ABI1 and ABI2 were upregulated, whereas that of downstream genes ABI3 and ABI5 were downregulated in both TaAIP2A and TaAIP2B complemented lines upon ABA treatment. These results suggested that wheat AIP2s could negatively regulate the ABA signaling pathway and play important roles in seed germination, and thus wheat PHS resistance finally.
基金This work was supported by EU funding within the NextGenerationEU-MUR PNRR Extended Partnership Initiative on Emerging Infectious Diseases(Project No.PE00000007,INF-ACT)。
文摘Computational methods have significantly transformed biomedical research,offering a comprehensive exploration of disease mechanisms and molecular protein functions.This article reviews a spectrum of computational tools and network analysis databases that play a crucial role in identifying potential interactions and signaling networks contributing to the onset of disease states.The utilization of protein/gene interaction and genetic variation databases,coupled with pathway analysis can facilitate the identification of potential drug targets.By bridging the gap between molecular-level information and disease understanding,this review contributes insights into the impactful utilization of computational methods,paving the way for targeted interventions and therapeutic advancements in biomedical research.
基金Supported by National Nature Science Foundation of China,No.81960051,No.8217021743,and No.82160060Project of High–Level Innovative Talents of Guizhou Province,No.[2016]4034Construction Funding from Characteristic Key Laboratory of Guizhou Province,No.[2021]313.
文摘BACKGROUND Heart failure is a health burden responsible for high morbidity and mortality worldwide, and dilated cardiomyopathy(DCM) is one of the most common causes of heart failure. DCM is a disease of the heart muscle and is characterized by enlargement and dilation of at least one ventricle alongside impaired contractility with left ventricular ejection fraction < 40%. It is also associated with abnormalities in cytoskeletal proteins, mitochondrial ATP transporter, microvasculature, and fibrosis. However, the pathogenesis and potential biomarkers of DCM remain to be investigated.AIM To investigate the candidate genes and pathways involved in DCM patients.METHODS Two expression datasets(GSE3585 and GSE5406) were downloaded from the Gene Expression Omnibus database. The differentially expressed genes(DEGs) between the DCM patients and healthy individuals were identified using the R package “linear models for microarray data.” The pathways with common DEGs were analyzed via Gene Ontology(GO), Kyoto Encyclopedia of Genes and Genomes(KEGG), and gene set enrichment analyses. Moreover, a protein-protein interaction network(PPI) was constructed to identify the hub genes and modules. The MicroRNA Database was applied to predict the microRNAs(miRNAs) targeting the hub genes. Additionally, immune cell infiltration in DCM was analyzed using CIBERSORT.RESULTS In total, 97 DEGs(47 upregulated and 50 downregulated) were identified. GO analysis showed that the DEGs were mainly enriched in “response to growth factor,” “extracellular matrix,” and “extracellular matrix structural constituent.” KEGG pathway analysis indicated that the DEGs were mainly enriched in “protein digestion and absorption” and “interleukin 17(IL-17) signaling pathway.” The PPI network suggested that collagen type Ⅲ alpha 1 chain(COL3A1) and COL1A2 contribute to the pathogenesis of DCM. Additionally, visualization of the interactions between miRNAs and the hub genes revealed that hsa-miR-5682 and hsa-miR-4500 interacted with both COL3A1 and COL1A2, and thus these miRNAs might play roles in DCM. Immune cell infiltration analysis revealed that DCM patients had more infiltrated plasma cells and fewer infiltrated B memory cells, T follicular helper cells, and resting dendritic cells.CONCLUSION COL1A2 and COL3A1 and their targeting miRNAs, hsa-miR-5682 and hsa-miR-4500, may play critical roles in the pathogenesis of DCM, which are closely related to the IL-17 signaling pathway and acute inflammatory response. These results may provide useful clues for the diagnosis and treatment of DCM.
文摘乳腺癌脑转移(breast cancer brain metastasis,BCBM)的发病机制尚未明确。为了探究BCBM的发病机制,对BCBM差异表达基因的生物学功能进行研究并筛选关键调控基因。从基因表达综合数据库(gene expression omnibus,GEO)下载4个BCBM基因表达谱数据(GSE12237、GSE100534、GSE125989以及GSE43837),采用R语言筛选差异表达基因,采用富集分析包括基因本体分析(gene ontology,GO)和京都基因与基因组百科全书分析(Kyoto encyclopedia of genes and genomes,KEGG)进行生物学功能分析,采用STRING和Cytoscape分析蛋白质相互作用网络,采用Kaplan-Meier进行生存分析。结果表明,同时存在于2个及以上基因表达谱数据中的差异表达基因261个,GO分析主要涉及细胞外基质组织、细胞外结构组织等生物过程,细胞外基质结构组成、胶原结合等分子功能,含有胶原的细胞外基质、胶原蛋白三聚物等细胞组分;KEGG分析主要涉及蛋白质消化和吸收、局部黏附等通路。蛋白质相互作用网络分析得到9个关键调控基因,其中,DCN、COL6A1与BCBM的生存率显著相关,可作为潜在的BCBM关键调控基因,并为BCBM分子机制的研究提供思路。