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1.
BMC Plant Biol ; 21(1): 304, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193039

RESUMO

BACKGROUND: The production of cereal crops is frequently affected by diseases caused by Fusarium graminearum and Magnaporthe oryzae, two devastating fungal pathogens. To improve crop resistance, many studies have focused on understanding the mechanisms of host defense against these two fungi individually. However, our knowledge of the common and different host defenses against these pathogens is very limited. RESULTS: In this study, we employed Brachypodium distachyon as a model for cereal crops and performed comparative transcriptomics to study the dynamics of host gene expression at different infection stages. We found that infection with either F. graminearum or M. oryzae triggered massive transcriptomic reprogramming in the diseased tissues. Numerous defense-related genes were induced with dynamic changes during the time course of infection, including genes that function in pattern detection, MAPK cascade, phytohormone signaling, transcription, protein degradation, and secondary metabolism. In particular, the expression of jasmonic acid signaling genes and proteasome component genes were likely specifically inhibited or manipulated upon infection by F. graminearum. CONCLUSIONS: Our analysis showed that, although the affected host pathways are similar, their expression programs and regulations are distinct during infection by F. graminearum and M. oryzae. The results provide valuable insight into the interactions between B. distachyon and two important cereal pathogens.


Assuntos
Ascomicetos/fisiologia , Brachypodium/genética , Brachypodium/microbiologia , Fusarium/fisiologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Ontologia Genética , Redes Reguladoras de Genes , Interações Hospedeiro-Patógeno/genética , Doenças das Plantas/microbiologia , Mapas de Interação de Proteínas/genética
2.
Medicine (Baltimore) ; 100(27): e26197, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34232166

RESUMO

ABSTRACT: To explore the possible molecular mechanism of reproductive toxicity of Tripterygium wilfordii from the perspective of network pharmacology and bioinformatics.The compounds of T wilfordii were obtained by querying the relevant Chinese medicine database, the effective compounds were screened and the corresponding targets were obtained, and then compared with the reproductive toxicities related to disease targets obtained from the disease gene database to infer the potential toxic targets of reproductive toxicity of T wilfordii. Then, the key targets of reproductive toxicity of T wilfordii were screened using Search Tool for the Retrieval of Interacting Genes/Protein and Cytoscape. The gene ontology function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, as well as module analysis, were performed on the key targets using Database for Annotation, Visualization, and Integrated Discovery and Cytoscape, respectively. Finally, the network between effective compounds-toxic targets was conducted to see how the compounds interacted.A total of 48 effective compounds and 482 potential toxic targets related to the reproductive toxicity of T wilfordii were screened. The enrichment analysis results showed that the key targets were mainly enriched in biological processes such as response to drug, ionotropic glutamate receptor signaling pathway, and KEGG pathways such as neuroactive ligand-receptor interaction, cAMP signaling pathway. In the protein-protein interaction network of potential toxic targets, there were 78 key targets such as TP53, INS, IL6, AGT, ADCY3, and so on. Enrichment analysis of the top module with 19 genes from module analysis indicated that T wilfordii might cause reproductive toxicity by gene ontology terms and KEGG pathways such as regulation of vasoconstriction, G-protein coupled receptor signaling pathway, inflammatory response, cAMP signaling pathway, and so on. In the network between effective compounds of T wilfordii and key targets, there were 5 compounds with high degree including Tingenone, Wilfordic Acid, Abruslactone A, Nobilin, and Wilforlide B.The complex molecular mechanism of reproductive toxicity of T wilfordii can be preliminarily elucidated with the help of the network pharmacology method, and the analysis results can provide some reference for the further mechanism research of reproductive toxicity of T wilfordii.


Assuntos
Mapas de Interação de Proteínas/genética , Tripterygium/toxicidade , Medicamentos de Ervas Chinesas/efeitos adversos , Ontologia Genética , Humanos , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Transdução de Sinais
3.
Medicine (Baltimore) ; 100(27): e26428, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34232175

RESUMO

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a common human malignancy worldwide. The tumorigenesis mechanism in ESCC is unclear. MATERIALS AND METHODS: To explore potential therapeutic targets for ESCC, we analyzed 3 microarray datasets (GSE20347, GSE38129, and GSE67269) derived from the gene expression omnibus (GEO) database. Then, the GEO2R tool was used to screen out differently expressed genes (DEGs) between ESCC and normal tissue. Gene ontology function and kyoto encyclopedia of genes and genomes pathway enrichment analysis were performed using the database for annotation, visualization and integrated discovery to identify the pathways and functional annotation of DEGs. Protein-protein interaction of these DEGs was analyzed based on the search tool for the retrieval of interacting genes database and visualized by Cytoscape software. In addition, we used encyclopedia of RNA interactomes (ENCORI), gene expression profiling interactive analysis (GEPIA), and the human protein atlas to confirm the expression of hub genes in ESCC. Finally, GEPIA was used to evaluate the prognostic value of hub genes expression in ESCC patients and we estimated the associations between hub genes expression and immune cell populations (B Cell, CD8+ T Cell, CD4+ T Cell, Macrophage, Neutrophil, and Dendritic Cell) in esophageal carcinoma (ESCA) using tumor immune estimation resource (TIMER). RESULTS: In this study, 707 DEGs (including 385 upregulated genes and 322 downregulated genes) and 6 hub genes (cyclin B1 [CCNB1], cyclin dependent kinase 1 [CDK1], aurora kinase A [AURKA], ubiquitin conjugating enzyme E2C [UBE2C], cyclin A2 [CCNA2], and cell division cycle 20 [CDC20]) were identified. All of the 6 hub genes were highly expressed in ESCC tissues. Among of them, only CCNB1 and CDC20 were associated with stage of ESCC and all of them were not associated with survival time of patients. CONCLUSION: DEGs and hub genes were confirmed in our study, providing a thorough, scientific and comprehensive research goals for the pathogenesis of ESCC.


Assuntos
Biologia Computacional/métodos , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , DNA de Neoplasias/genética , DNA de Neoplasias/metabolismo , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/metabolismo , Humanos , Mapas de Interação de Proteínas/genética
4.
Medicine (Baltimore) ; 100(27): e26530, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34232189

RESUMO

ABSTRACT: Endometriosis is associated with dysmenorrhea, chronic pelvic pain, and infertility. The specific mechanism of endometriosis remains unclear. The aim of this study was to apply a bioinformatics approach to reveal related pathways or genes involved in the development of endometriosis.The gene expression profiles of GSE25628, GSE5108, and GSE7305 were downloaded from the gene expression omnibus (GEO) database. Differentially expressed gene (DEG) analysis was performed using GEO2R. The database for annotation, visualization, and integrated discovery (DAVID) was utilized to analyze the functional enrichment, gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathway of the differentially expressed genes. A protein-protein interaction (PPI) network was constructed and module analysis was performed using search tool for the retrieval of interacting genes and cytoscape.A total of 119 common differentially expressed genes were extracted, consisting of 51 downregulated genes and 68 upregulated genes. The enriched functions and pathways of the DEGs and hub genes include DNA strand separation, cellular proliferation, degradation of the extracellular matrix, encoding of smooth muscle myosin as a major contractile protein, exiting the proliferative cycle and entering quiescence, growth regulation, and implication in a wide variety of biological processes.A bioinformatics approach combined with cell experiments in this study revealed that identifying DEGs and hub genes leads to better understanding of the molecular mechanisms underlying the progression of endometriosis, and efficient biomarkers underlying this pathway need to be further investigated.


Assuntos
Biologia Computacional/métodos , Endometriose/genética , Regulação Neoplásica da Expressão Gênica , Mapas de Interação de Proteínas/genética , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Endometriose/metabolismo , Feminino , Ontologia Genética , Humanos
5.
Int J Mol Sci ; 22(11)2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34205207

RESUMO

Since dysregulation of intracellular calcium (Ca2+) levels is a common occurrence in neurodegenerative diseases, including Alzheimer's disease (AD), the study of proteins that can correct neuronal Ca2+ dysregulation is of great interest. In previous work, we have shown that plasma membrane Ca2+-ATPase (PMCA), a high-affinity Ca2+ pump, is functionally impaired in AD and is inhibited by amyloid-ß peptide (Aß) and tau, two key components of pathological AD hallmarks. On the other hand, sorcin is a Ca2+-binding protein highly expressed in the brain, although its mechanism of action is far from being clear. Sorcin has been shown to interact with the intracellular sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA), and other modulators of intracellular Ca2+ signaling, such as the ryanodine receptor or presenilin 2, which is closely associated with AD. The present work focuses on sorcin in search of new regulators of PMCA and antagonists of Aß and tau toxicity. Results show sorcin as an activator of PMCA, which also prevents the inhibitory effects of Aß and tau on the pump, and counteracts the neurotoxicity of Aß and tau by interacting with them.


Assuntos
Doença de Alzheimer/genética , Proteínas de Ligação ao Cálcio/genética , ATPases Transportadoras de Cálcio da Membrana Plasmática/genética , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/genética , Encéfalo/metabolismo , Encéfalo/patologia , Cálcio/metabolismo , Sinalização do Cálcio/genética , Humanos , Neurônios/metabolismo , Neurônios/patologia , ATPases Transportadoras de Cálcio da Membrana Plasmática/metabolismo , Presenilina-2/genética , Ligação Proteica/genética , Mapas de Interação de Proteínas/genética , Proteínas tau/genética
6.
Nat Commun ; 12(1): 3564, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-34117231

RESUMO

Protein-protein interactions govern most cellular pathways and processes, and multiple technologies have emerged to systematically map them. Assessing the error of interaction networks has been a challenge. Crosslinking mass spectrometry is currently widening its scope from structural analyses of purified multi-protein complexes towards systems-wide analyses of protein-protein interactions (PPIs). Using a carefully controlled large-scale analysis of Escherichia coli cell lysate, we demonstrate that false-discovery rates (FDR) for PPIs identified by crosslinking mass spectrometry can be reliably estimated. We present an interaction network comprising 590 PPIs at 1% decoy-based PPI-FDR. The structural information included in this network localises the binding site of the hitherto uncharacterised protein YacL to near the DNA exit tunnel on the RNA polymerase.


Assuntos
Espectrometria de Massas/métodos , Mapeamento de Interação de Proteínas/métodos , Mapas de Interação de Proteínas , Escherichia coli/genética , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/metabolismo , Mapas de Interação de Proteínas/genética , Proteoma
7.
Medicine (Baltimore) ; 100(25): e26499, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160465

RESUMO

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple organ damage and the production of a variety of autoantibodies. The pathogenesis of SLE has not been fully defined, and it is difficult to treat. Our study aimed to identify candidate genes that may be used as biomarkers for the screening, diagnosis, and treatment of SLE. METHODS: We used the GEO2R tool to identify the differentially expressed genes (DEGs) in SLE-related datasets retrieved from the Gene Expression Omnibus (GEO). In addition, we also identified the biological functions of the DEGs by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Additionally, we constructed protein-protein interaction (PPI) networks to identify hub genes, as well as the regulatory network of transcription factors related to DEGs. RESULTS: Two datasets were identified for use from the GEO (GSE50772, GSE4588), and 34 up-regulated genes and 4 down-regulated genes were identified by GEO2R. Pathway analysis of the DEGs revealed enrichment of the interferon alpha/beta signaling pathway; GO analysis was mainly enriched in response to interferon alpha, regulation of ribonuclease activity. PPIs were constructed through the STRING database and 14 hub genes were selected and 1 significant module (score = 12.923) was obtained from the PPI network. Additionally, 11 key transcription factors that interacted closely with the 14 hub DEGs were identified from the gene transcription factor network. CONCLUSIONS: Bioinformatic analysis is an effective tool for screening the original genomic data in the GEO database, and a large number of SLE-related DEGs were identified. The identified hub DEGs may be potential biomarkers of SLE.


Assuntos
Regulação da Expressão Gênica/imunologia , Redes Reguladoras de Genes , Lúpus Eritematoso Sistêmico/genética , Fatores de Transcrição/metabolismo , Biomarcadores/análise , Biologia Computacional , Conjuntos de Dados como Assunto , Perfilação da Expressão Gênica , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Análise de Sequência com Séries de Oligonucleotídeos , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas/genética , Transdução de Sinais/genética , Transdução de Sinais/imunologia
8.
Aging (Albany NY) ; 13(10): 13626-13643, 2021 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-34091441

RESUMO

BACKGROUND: E2F2 is a member of the E2F transcription factor family and has important but not fully understood biological functions in cancers. The biological role of E2F2 in gastric cancer (GC) also remains unclear. METHODS: We examined the expression levels of E2F2 in GC using publicly available datasets such as TIMER, Oncomine, GEPIA, UALCAN, etc., and in our patient cohort, using quantitative real-time PCR, western blotting, and immunohistochemistry. We further investigated the effects of E2F2 on phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling, autophagy, and the migration and invasion of GC cells by the wound healing assay, Transwell assay and transmission electron microscopy. RESULTS: E2F2 was highly expressed in both GC tissues and cells compared with normal gastric tissues/cells. High E2F2 expression was associated with poor overall survival (OS). In addition, the expression of E2F2 in GC was strongly correlated with a variety of immune markers. E2F2 overexpression promoted the migration and invasiveness of GC cells in vitro through inhibition of PI3K/Akt/mTOR-mediated autophagy. CONCLUSION: High E2F2 expression was associated with the characteristics of invasive tumors and poor prognosis. E2F2 also had potential modulatory effects on tumor immunity. We discovered a novel function of E2F2 in the regulation of PI3K/Akt/mTOR-mediated autophagy and the downstream processes of cell migration and invasion.


Assuntos
Autofagia , Fator de Transcrição E2F2/antagonistas & inibidores , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Neoplasias Gástricas/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Idoso , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Metilação de DNA/genética , Fator de Transcrição E2F2/genética , Fator de Transcrição E2F2/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Genoma Humano , Humanos , Masculino , Análise Multivariada , Invasividade Neoplásica , Prognóstico , Receptor de Morte Celular Programada 1/metabolismo , Mapas de Interação de Proteínas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Regulação para Cima/genética
9.
Clin Interv Aging ; 16: 1071-1084, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34140767

RESUMO

Purpose: Carotid atherosclerosis is a kind of systemic atherosclerosis in the carotid arteries. However, the efficiency of treatment is insufficient. Therefore, it is urgent to find therapeutic targets and deepen the understanding of carotid atherosclerosis. Materials and Methods: In this study, we analyzed differentially expressed genes (DEGs) between atheroma plaque and macroscopically intact tissue (control samples). Furthermore, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genomes (KEGG) enrichment analysis based on the DEGs. Four methods were used to identify the hub genes in the protein-protein interaction networks of the DEGs. Furthermore, we also performed network module analysis to reveal carotid atherosclerosis-related gene modules and biological functions. Results: The enrichment results showed that the biological functions were related to inflammation, immunity, chemokine and cell adhesion molecule, such as PIK-Akt signaling pathway, Rap1 signaling pathway, MAPK signaling pathway, NOD-like receptor signaling pathway and B cell receptor signaling pathway. In addition, we screened the hub genes. A total of 16 up-regulated genes (C3AR1, CCR1, CCR2, CD33, CD53, CXCL10, CXCL8, CXCR4, CYBB, FCER1G, FPR2, ITGAL, ITGAM, ITGAX, ITGB2, and LILRB2) were identified as hub genes. A total of 5 gene modules were obtained. We found that biological functions obtained for each cluster were mostly related to immunity, chemokines and cell adhesion molecules. Conclusion: The present study identified key DEGs in atheroma plaque compared with control samples. The key genes involved in the development of carotid atherosclerosis may provide valuable therapeutic targets for carotid atherosclerosis.


Assuntos
Doenças das Artérias Carótidas/genética , Perfilação da Expressão Gênica/métodos , Mapas de Interação de Proteínas/genética , Artérias Carótidas/patologia , Doenças das Artérias Carótidas/metabolismo , Biologia Computacional/métodos , Regulação para Baixo/genética , Ontologia Genética/estatística & dados numéricos , Redes Reguladoras de Genes , Humanos , Placa Aterosclerótica , Transdução de Sinais , Regulação para Cima
10.
J Cancer Res Clin Oncol ; 147(8): 2199-2207, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34115239

RESUMO

Colorectal cancer is an important public health concern leading to significant cancer associate mortality. A vast majority of colon cancer arises from polyp which later follows adenoma, adenocarcinoma, and carcinoma sequence. This whole process takes several years to complete and recent genomic and proteomic technologies are identifying several targets involved in each step of polyp to carcinoma transformation in a large number of studies. Current text presents interaction network of targets involved in polyp to carcinoma transformation. In addition, important targets involved in each step according to network biological parameters are also presented. The functional overrepresentation analysis of each step targets and common top biological processes and pathways involved in carcinoma indicate several insights about this whole mechanism. Interaction networks indicate TP53, AKT1, GAPDH, INS, EGFR, and ALB as the most important targets commonly involved in polyp to carcinoma sequence. Though several important pathways are known to be involved in CRC, the central common involvement of PI3K-AKT indicates its potential for devising CRC management strategies. The common and central targets and pathways involved in polyp to carcinoma progression can shed light on its mechanism and potential management strategies. The data-driven approach aims to add valuable inputs to the mechanism of the years-long polyp-carcinoma sequence.


Assuntos
Carcinoma/prevenção & controle , Transformação Celular Neoplásica , Neoplasias do Colo/prevenção & controle , Pólipos do Colo/terapia , Terapia de Alvo Molecular/métodos , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/prevenção & controle , Adenoma/genética , Adenoma/metabolismo , Adenoma/patologia , Adenoma/prevenção & controle , Pólipos Adenomatosos/genética , Pólipos Adenomatosos/metabolismo , Pólipos Adenomatosos/patologia , Pólipos Adenomatosos/prevenção & controle , Antineoplásicos/uso terapêutico , Carcinoma/genética , Carcinoma/metabolismo , Carcinoma/patologia , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Pólipos do Colo/genética , Pólipos do Colo/metabolismo , Pólipos do Colo/patologia , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Redes Reguladoras de Genes/fisiologia , Genes de Troca/efeitos dos fármacos , Humanos , Mapas de Interação de Proteínas/efeitos dos fármacos , Mapas de Interação de Proteínas/genética , Proteômica , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
11.
Int J Mol Sci ; 22(9)2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-34066408

RESUMO

WUSCHEL-related homeobox (WOX) transcription factors (TFs) are well known for their role in plant development but are rarely studied in citrus. In this study, we identified 11 putative genes from the sweet orange genome and divided the citrus WOX genes into three clades (modern/WUSCHEL(WUS), intermediate, and ancient). Subsequently, we performed syntenic relationship, intron-exon organization, motif composition, and cis-element analysis. Co-expression analysis based on RNA-seq and tissue-specific expression patterns revealed that CsWOX gene expression has multiple intrinsic functions. CsWUS homolog of AtWUS functions as a transcriptional activator and binds to specific DNA. Overexpression of CsWUS in tobacco revealed dramatic phenotypic changes, including malformed leaves and reduced gynoecia with no seed development. Silencing of CsWUS in lemon using the virus-induced gene silencing (VIGS) system implied the involvement of CsWUS in cells of the plant stem. In addition, CsWUS was found to interact with CsCYCD3, an ortholog in Arabidopsis (AtCYCD3,1). Yeast one-hybrid screening and dual luciferase activity revealed that two TFs (CsRAP2.12 and CsHB22) bind to the promoter of CsWUS and regulate its expression. Altogether, these results extend our knowledge of the WOX gene family along with CsWUS function and provide valuable findings for future study on development regulation and comprehensive data of WOX members in citrus.


Assuntos
Citrus sinensis/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Família Multigênica , Proteínas de Plantas/genética , Simulação por Computador , Sequência Conservada/genética , Éxons/genética , Flores/genética , Inativação Gênica , Íntrons/genética , Motivos de Nucleotídeos/genética , Fenótipo , Filogenia , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas , Mapas de Interação de Proteínas/genética , Frações Subcelulares/metabolismo , Sintenia/genética , Tabaco/genética , Água
12.
Aging (Albany NY) ; 13(12): 16445-16470, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34148032

RESUMO

Acute myeloid leukemia (AML) is a group of heterogeneous hematological malignancies. We identified key genes as ITGAM and lncRNA ITGB2-AS1 through different bioinformatics tools. Furthermore, qPCR was performed to verify the expression level of essential genes in clinical samples. Retrospective research on 179 AML cases was used to investigate the relationship between the expression of ITGAM and the characteristics of AML. The critical gene relationship with immune infiltration in AML was estimated. The clinical validation and prognostic investigation showed that ITGAM, PPBP, and ITGB2-AS1 are highly expressed in AML (P < 0.001) and significantly associated with the overall survival in AML. Moreover, the retrospective research on 179 clinical cases showed that positive expression of ITGAM is substantially related to AML classification (P < 0.001), higher count of white blood cells (P < 0.01), and poor chemotherapy outcome (P < 0.05). Furthermore, based on grouping ITGAM as the high and low expression in TCGA-LAML profile, we found that genes in the highly expressed ITGAM group are mainly involved in immune infiltration and inflammation-related signaling pathways. Finally, we discovered that the expression level of ITGAM and lncRNA ITGB2-AS1 are not just closely related to the immune score and stromal score (P < 0.001) but also significantly positively correlated with various Immune signatures in AML (P < 0.001), indicating the association of these genes with immunosuppression in AML. The prediction of candidate drugs indicated that certain immunosuppressive drugs have potential therapeutic effects for AML. The critical genes could be used as potential biomarkers to evaluate the survival and prognosis of AML.


Assuntos
Perfilação da Expressão Gênica , Regulação Leucêmica da Expressão Gênica , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/imunologia , Feminino , Ontologia Genética , Redes Reguladoras de Genes , Genes Essenciais , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Mapas de Interação de Proteínas/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Curva ROC , Reprodutibilidade dos Testes , Transdução de Sinais/genética , Transcriptoma/genética , Resultado do Tratamento , Microambiente Tumoral/genética
13.
Aging (Albany NY) ; 13(12): 16425-16444, 2021 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-34156352

RESUMO

To identify novel prognostic and therapeutic targets for osteosarcoma patients, we compared the gene expression profiles of osteosarcoma and control tissues from the GSE42352 dataset in the Gene Expression Omnibus. Differentially expressed genes were subjected to Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Gene Set Enrichment and protein-protein interaction network analyses. Survival curve analyses indicated that osteosarcoma patients with lower mRNA levels of cyclin-dependent kinase 1 (CDK1) and topoisomerase II alpha had better prognoses. Various computer-aided techniques were used to identify potential CDK1 inhibitors for osteosarcoma patients, and PHA-793887 was predicted to be a safe drug with a high binding affinity for CDK1. In vitro, MTT and colony formation assays demonstrated that PHA-793887 reduced the viability and clonogenicity of osteosarcoma cells, while a scratch assay suggested that PHA-793887 impaired the migration of these cells. Flow cytometry experiments revealed that PHA-793887 dose-dependently induced apoptosis in osteosarcoma cells. Western blotting and enzyme-linked immunosorbent assays indicated that CDK1 expression in osteosarcoma cells declined with increasing PHA-793887 concentrations. These results suggest that PHA-793887 could be a promising new treatment for osteosarcoma.


Assuntos
Biologia Computacional , Simulação de Acoplamento Molecular , Osteossarcoma/tratamento farmacológico , Pirazóis/uso terapêutico , Pirróis/uso terapêutico , Sítios de Ligação , Proteína Quinase CDC2/antagonistas & inibidores , Proteína Quinase CDC2/metabolismo , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes/efeitos dos fármacos , Humanos , Ligantes , Osteossarcoma/genética , Osteossarcoma/patologia , Mapas de Interação de Proteínas/genética , Inibidores de Proteínas Quinases/efeitos adversos , Pirazóis/química , Pirazóis/farmacologia , Pirróis/química , Pirróis/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Análise de Sobrevida
14.
Aging (Albany NY) ; 13(12): 16513-16526, 2021 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-34157681

RESUMO

Colon adenocarcinoma (COAD) is a common cancer of the digestive system. It's high morbidity and mortality make it one of the leading causes of cancer deaths. In this study, we studied the microenvironment of colon cancer to find new diagnostic markers and immunotherapy targets for colon cancer. Tumor purity of colon cancer samples in TCGA database were obtained by ESTIMATE algorithm. Then, we analyzed the association of Immune, Stromal, and Estimate scores with tumor prognosis and clinicopathological features. By comparing the gene expression profiles between tumor and normal samples, the high and low immune score groups, 117 intersecting differentially expressed genes (DEGs) were obtained. The function, molecular pathway, and prognostic value of these 117 DEGs pointed toward the importance of deoxyribonuclease 1-like 3 (DNASE1L3). Validation results from multiple databases showed low expression of DNASE1L3 in colon cancer. A single GSEA and correlation analysis of immune cells indicated that DNASE1L3 was closely related to immunity. The low expression of DNASE1L3 in colon cancer samples was measured with qRT-PCR. The scratch and cell proliferation experiments suggested that DNASE1L3 may affect cell migration. Therefore, we concluded that DNASE1L3 might be a biomarker associated with prognosis and immune infiltration in colon cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias do Colo/imunologia , Endodesoxirribonucleases/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Bases de Dados Genéticas , Endodesoxirribonucleases/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Prognóstico , Mapas de Interação de Proteínas/genética , Reprodutibilidade dos Testes , Análise de Sobrevida , Transcriptoma
15.
Aging (Albany NY) ; 13(12): 16713-16732, 2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-34170849

RESUMO

Ferroptosis, a form of programmed cell death induced by excess iron-dependent lipid peroxidation product accumulation, plays a critical role in cancer. However, there are few reports about ferroptosis in endometrial cancer (EC). This article explores the relationship between ferroptosis-related gene (FRG) expression and prognosis in EC patients. One hundred thirty-five FRGs were obtained by mining the literature, retrieving GeneCards and analyzing 552 malignant uterine corpus endometrial carcinoma (UCEC) samples, which were randomly assigned to training and testing groups (1:1 ratio), and 23 normal samples from The Cancer Genome Atlas (TCGA). We established a signature using eight screened FRGs (MDM2, GPX4, PRKAA2, PRNP, SLC11A2, ATP5MC3, PHKG2 and ACO1) related to overall survival using LASSO regression analysis. The samples were divided into low- and high-risk subgroups according to the median risk score. Kaplan-Meier survival curves showed that the low-risk group had better OS. ROC curves showed that this signature performed well in predicting OS (1-, 2-, 3-, and 5-year AUCs of 0.676, 0.775, 0.797, and 0.826, respectively). We systematically analyzed the immune infiltrating profile in UCEC samples from TCGA. Overall, our study identified a novel prognostic signature of 8 FRGs that can potentially predict the prognosis of EC.


Assuntos
Neoplasias do Endométrio/genética , Neoplasias do Endométrio/imunologia , Ferroptose/genética , Perfilação da Expressão Gênica , Linfócitos do Interstício Tumoral/metabolismo , Estudos de Coortes , Bases de Dados Genéticas , Feminino , Regulação Neoplásica da Expressão Gênica , Variação Genética , Humanos , Anotação de Sequência Molecular , Análise de Componente Principal , Prognóstico , Mapas de Interação de Proteínas/genética , Reprodutibilidade dos Testes , Fatores de Risco
16.
Aging (Albany NY) ; 13(12): 16577-16599, 2021 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-34175839

RESUMO

Since the imbalance of gene expression has been demonstrated to tightly related to breast cancer (BRCA) genesis and growth, common genes expressed of BRCA were screened to explore the essence in-between. In current work, most common differentially expressed genes (DEGs) in various subtypes of BRCA were identified. Functional enrichment analysis illustrated the driving factor of deactivation of the cell cycle and the oocyte meiosis, which critically triggers the development of BRCA. Herein, we constructed a 12-gene prognostic risk model relative to differential gene expression. Subsequently, the K-M curves, analysis on time-ROC curve and Cox regression were performed to assess this risk model by determining the respective prognostic value, and the prediction performance were ascertained for both training and validation cohorts. In addition, multivariate Cox regression was analysed to reveal the independence between risk score and prognostic stage, and the accuracy and sensitivity of prognosis are particularly improved after clinical indicators are included into the analysis. In summary, this study offers novel insights into the imbalance of gene expression within BRCA, and highlights 12 selected genes associated with patient prognosis. The risk model can help individualize treatment for patients at different risks, and propose precise strategies and treatments for BRCA therapy.


Assuntos
Neoplasias da Mama/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Modelos Biológicos , Bases de Dados Genéticas , Feminino , Ontologia Genética , Humanos , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Mapas de Interação de Proteínas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Risco , Análise de Sobrevida
17.
Aging (Albany NY) ; 13(9): 12865-12895, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33946043

RESUMO

Hepatitis C virus-associated HCC (HCV-HCC) is a prevalent malignancy worldwide and the molecular mechanisms are still elusive. Here, we screened 240 differentially expressed genes (DEGs) of HCV-HCC from Gene expression omnibus (GEO) and the Cancer Genome Atlas (TCGA), followed by weighted gene coexpression network analysis (WGCNA) to identify the most significant module correlated with the overall survival. 10 hub genes (CCNB1, AURKA, TOP2A, NEK2, CENPF, NUF2, CDKN3, PRC1, ASPM, RACGAP1) were identified by four approaches (Protein-protein interaction networks of the DEGs and of the significant module by WGCNA, and diagnostic and prognostic values), and their abnormal expressions, diagnostic values, and prognostic values were successfully verified. A four hub gene-based prognostic signature was built using the least absolute shrinkage and selection operator (LASSO) algorithm and a multivariate Cox regression model with the ICGC-LIRI-JP cohort (N =112). Kaplan-Meier survival plots (P = 0.0003) and Receiver Operating Characteristic curves (ROC = 0.778) demonstrated the excellent predictive potential for the prognosis of HCV-HCC. Additionally, upstream regulators including transcription factors and miRNAs of hub genes were predicted, and candidate drugs or herbs were identified. These findings provide a firm basis for the exploration of the molecular mechanism and further clinical biomarkers development of HCV-HCC.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/diagnóstico , Hepatite C Crônica/patologia , Neoplasias Hepáticas/diagnóstico , RNA Mensageiro/metabolismo , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/virologia , Biologia Computacional , Conjuntos de Dados como Assunto , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Hepatite C Crônica/genética , Hepatite C Crônica/virologia , Humanos , Estimativa de Kaplan-Meier , Fígado/patologia , Fígado/virologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/virologia , MicroRNAs/metabolismo , Valor Preditivo dos Testes , Prognóstico , Mapas de Interação de Proteínas/genética , RNA Mensageiro/genética , Medição de Risco/métodos , Fatores de Transcrição/metabolismo , Transcriptoma/genética
18.
Aging (Albany NY) ; 13(9): 12733-12747, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33973530

RESUMO

While acknowledging carotid atherosclerosis (CAS) as a risk factor for ischemic stroke, reports on its pathogenesis are scarce. This study aimed to explore the potential mechanism of CAS through RNA-seq data analysis. Carotid intima tissue samples from CAS patients and healthy subjects were subjected to RNA-seq analysis, which yielded, 1,427 differentially expressed genes (DEGs) related to CAS. Further, enrichment analysis (Gene Ontology, KEGG pathway, and MOCDE analysis) was performed on the DEGs. Hub genes identified via the protein-protein interaction network (PPI) were then analyzed using TRRUST, DisGeNET, PaGenBase, and CMAP databases. Results implicated inflammation and immunity in the pathogenesis of CAS. Also, lung disease was associated with CAS. Hub genes were expressed in multiple diseases, mainly regulated by RELA and NFKB1. Moreover, three small-molecule compounds were found via the CMAP database for management of CAS; hub genes served as potential targets. Collectively, inflammation and immunity are the potential pathological mechanisms of CAS. This study implicates CeForanide, Chenodeoxycholic acid, and 0317956-0000 as potential drug candidates for CAS treatment.


Assuntos
Doenças das Artérias Carótidas/genética , Regulação da Expressão Gênica/imunologia , Mapas de Interação de Proteínas/genética , Doenças das Artérias Carótidas/tratamento farmacológico , Doenças das Artérias Carótidas/imunologia , Doenças das Artérias Carótidas/patologia , Estudos de Casos e Controles , Cefamandol/análogos & derivados , Cefamandol/farmacologia , Cefamandol/uso terapêutico , Ácido Quenodesoxicólico/farmacologia , Ácido Quenodesoxicólico/uso terapêutico , Biologia Computacional , Conjuntos de Dados como Assunto , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Mapas de Interação de Proteínas/efeitos dos fármacos , RNA-Seq , Túnica Íntima/patologia
19.
Genomics ; 113(4): 2158-2170, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34004284

RESUMO

Recently, the SARS-CoV-2 variants from the United Kingdom (UK), South Africa, and Brazil have received much attention for their increased infectivity, potentially high virulence, and possible threats to existing vaccines and antibody therapies. The question remains if there are other more infectious variants transmitted around the world. We carry out a large-scale study of 506,768 SARS-CoV-2 genome isolates from patients to identify many other rapidly growing mutations on the spike (S) protein receptor-binding domain (RBD). We reveal that essentially all 100 most observed mutations strengthen the binding between the RBD and the host angiotensin-converting enzyme 2 (ACE2), indicating the virus evolves toward more infectious variants. In particular, we discover new fast-growing RBD mutations N439K, S477N, S477R, and N501T that also enhance the RBD and ACE2 binding. We further unveil that mutation N501Y involved in United Kingdom (UK), South Africa, and Brazil variants may moderately weaken the binding between the RBD and many known antibodies, while mutations E484K and K417N found in South Africa and Brazilian variants, L452R and E484Q found in India variants, can potentially disrupt the binding between the RBD and many known antibodies. Among these RBD mutations, L452R is also now known as part of the California variant B.1.427. Finally, we hypothesize that RBD mutations that can simultaneously make SARS-CoV-2 more infectious and disrupt the existing antibodies, called vaccine escape mutations, will pose an imminent threat to the current crop of vaccines. A list of most likely vaccine escape mutations is given, including S494P, Q493L, K417N, F490S, F486L, R403K, E484K, L452R, K417T, F490L, E484Q, and A475S. Mutation T478K appears to make the Mexico variant B.1.1.222 the most infectious one. Our comprehensive genetic analysis and protein-protein binding study show that the genetic evolution of SARS-CoV-2 on the RBD, which may be regulated by host gene editing, viral proofreading, random genetic drift, and natural selection, gives rise to more infectious variants that will potentially compromise existing vaccines and antibody therapies.


Assuntos
Enzima de Conversão de Angiotensina 2/genética , Vacinas contra COVID-19/genética , COVID-19/genética , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/virologia , Vacinas contra COVID-19/efeitos adversos , Humanos , Mutação , Ligação Proteica/genética , Mapas de Interação de Proteínas/genética , SARS-CoV-2/patogenicidade
20.
Plant Cell Rep ; 40(7): 1247-1267, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34028582

RESUMO

KEY MESSAGE: PSV infection changed the abundance of host plant's transcripts and proteins associated with various cellular compartments, including ribosomes, chloroplasts, mitochondria, the nucleus and cytosol, affecting photosynthesis, translation, transcription, and splicing. Virus infection is a process resulting in numerous molecular, cellular, and physiological changes, a wide range of which can be analyzed due to development of many high-throughput techniques. Plant RNA viruses are known to replicate in the cytoplasm; however, the roles of chloroplasts and other cellular structures in the viral replication cycle and in plant antiviral defense have been recently emphasized. Therefore, the aim of this study was to analyze the small RNAs, transcripts, proteins, and phosphoproteins affected during peanut stunt virus strain P (PSV-P)-Nicotiana benthamiana interactions with or without satellite RNA (satRNA) in the context of their cellular localization or functional connections with particular cellular compartments to elucidate the compartments most affected during pathogenesis at the early stages of infection. Moreover, the processes associated with particular cell compartments were determined. The 'omic' results were subjected to comparative data analyses. Transcriptomic and small RNA (sRNA)-seq data were obtained to provide new insights into PSV-P-satRNA-plant interactions, whereas previously obtained proteomic and phosphoproteomic data were used to broaden the analysis to terms associated with cellular compartments affected by virus infection. Based on the collected results, infection with PSV-P contributed to changes in the abundance of transcripts and proteins associated with various cellular compartments, including ribosomes, chloroplasts, mitochondria, the nucleus and the cytosol, and the most affected processes were photosynthesis, translation, transcription, and mRNA splicing. Furthermore, sRNA-seq and phosphoproteomic analyses indicated that kinase regulation resulted in decreases in phosphorylation levels. The kinases were associated with the membrane, cytoplasm, and nucleus components.


Assuntos
Cucumovirus/patogenicidade , Biologia de Sistemas/métodos , Tabaco/citologia , Tabaco/virologia , Núcleo Celular/genética , Núcleo Celular/virologia , Cloroplastos/genética , Cloroplastos/virologia , Citoesqueleto/genética , Citoesqueleto/virologia , Citosol/virologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Interações Hospedeiro-Patógeno/fisiologia , MicroRNAs , Nitrogênio/metabolismo , Fosfoproteínas/metabolismo , Células Vegetais/virologia , Doenças das Plantas/virologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Mapas de Interação de Proteínas/genética , RNA Satélite , Tabaco/genética
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