scholarly journals Expression and Gene Regulation Network of SOX9 in Skin Metastasis of Gastric Carcinoma Derived From One Special Patient

2021 ◽  
Author(s):  
Guofeng Chen ◽  
Jiyun Zhu ◽  
Tang Yang ◽  
Huifang Wang ◽  
Liegang Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Transcription Factors ◽  
Gastric Carcinoma ◽  
Survival Curve ◽  
Clinical Stage ◽  
Mrna Level ◽  
Skin Metastasis ◽  
The Cancer Genome Atlas ◽  
Sox9 Expression

Abstract BackgroundAn exceptional case of a patient with advanced gastric cancer is presented in this study, treated with multiple chemotherapy, radiotherapy and immune regimens, who exhibited regression of one metastatic lesion with concomitant progression of the other lesion during a treatment of PD-1 antibody period. MethodsUsing whole-exome sequencing, TBM, MSI/MSS, PD-1 positive or negative respond measurement, gene function, tumor expression, clinical stage, survival curve, pathopoiesia gene prediction, neoantigen score and immunogenomic approaches. ResultsWe found that SOX9 might mainly participate into the response process of PD-1 antibody in the right skin metastasis. Then, we used sequencing data from the Cancer Genome Atlas database and Gene Expression Omnibus, analyzing SOX9 expression and gene regulation networks in gastric carcinoma (GC). Expression and CNVs were analyzed using Oncomine and Gene Expression Profiling Interactive Analysis tools, at the same time, SOX9 alterations and related pathway were identified using cBioPortal. LinkedOmics and GeneMANIA were used to identify differential mRNA expression with SOX9 and to analyze Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. Gene enrichment analysis examined target networks of kinases, miRNAs, transcription factors and PPIs. The results show that SOX9 is overexpressed and the alteration type of SXO9 is mutation in GC. Expression of this gene coding protein is associated with biological interaction networks involving the cell dedifferentiation and WNT signaling process. Functional network analysis indicates that SOX9 mRNA level regulates the RNA process, DNA replication and cell cycle via pathways involving several cancer-related kinases, miRNAs and transcription factors, like casein kinase 2 alpha 1, cyclin dependent kinase 2, Mir296 and Mir214. ConclusionsOur results finally demonstrate that bioinformation analysis efficiently reveals online information of SOX9 expression and potential regulatory networks in GC, laying a foresight for further study of the role of SOX9 and a new PD-1 treatment predictor in gastric carcinogenesis.

scholarly journals Identification of an extracellular vesicle-related gene signature in the prediction of pancreatic cancer clinical prognosis

2020 ◽  
Vol 40 (12) ◽  
Author(s):  
Dafeng Xu ◽  
Yu Wang ◽  
Kailun Zhou ◽  
Jincai Wu ◽  
Zhensheng Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pancreatic Cancer ◽  
Immune Cells ◽  
Prognostic Value ◽  
Tumor Tissue ◽  
Clinical Stage ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Sequencing Data ◽  
Clinical Prognosis

Abstract Although extracellular vesicles (EVs) in body fluid have been considered to be ideal biomarkers for cancer diagnosis and prognosis, it is still difficult to distinguish EVs derived from tumor tissue and normal tissue. Therefore, the prognostic value of tumor-specific EVs was evaluated through related molecules in pancreatic tumor tissue. NA sequencing data of pancreatic adenocarcinoma (PAAD) were acquired from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC). EV-related genes in pancreatic cancer were obtained from exoRBase. Protein–protein interaction (PPI) network analysis was used to identify modules related to clinical stage. CIBERSORT was used to assess the abundance of immune and non-immune cells in the tumor microenvironment. A total of 12 PPI modules were identified, and the 3-PPI-MOD was identified based on the randomForest package. The genes of this model are involved in DNA damage and repair and cell membrane-related pathways. The independent external verification cohorts showed that the 3-PPI-MOD can significantly classify patient prognosis. Moreover, compared with the model constructed by pure gene expression, the 3-PPI-MOD showed better prognostic value. The expression of genes in the 3-PPI-MOD had a significant positive correlation with immune cells. Genes related to the hypoxia pathway were significantly enriched in the high-risk tumors predicted by the 3-PPI-MOD. External databases were used to verify the gene expression in the 3-PPI-MOD. The 3-PPI-MOD had satisfactory predictive performance and could be used as a prognostic predictive biomarker for pancreatic cancer.

scholarly journals Epigenetic manipulation of gene expression

2005 ◽  
Vol 169 (6) ◽  
pp. 847-857 ◽  
Author(s):  
Rudy L. Juliano ◽  
Vidula R. Dixit ◽  
Hyunmin Kang ◽  
Tai Young Kim ◽  
Yuko Miyamoto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Culture ◽  
Gene Regulation ◽  
Transcription Factors ◽  
Rna Interference ◽  
Antisense Oligonucleotide ◽  
Significant Progress ◽  
Direct Experience ◽  
Key Features ◽  
Epigenetic Manipulation

Cell biologists have been afforded extraordinary new opportunities for experimentation by the emergence of powerful technologies that allow the selective manipulation of gene expression. Currently, RNA interference is very much in the limelight; however, significant progress has also been made with two other approaches. Thus, antisense oligonucleotide technology is undergoing a resurgence as a result of improvements in the chemistry of these molecules, whereas designed transcription factors offer a powerful and increasingly convenient strategy for either up- or down-regulation of targeted genes. This mini-review will highlight some of the key features of these three approaches to gene regulation, as well as provide pragmatic guidance concerning their use in cell biological experimentation based on our direct experience with each of these technologies. The approaches discussed here are being intensely pursued in terms of possible therapeutic applications. However, we will restrict our comments primarily to the cell culture situation, only briefly alluding to fundamental differences between utilization in animals versus cells.

scholarly journals ANXA9 as a novel prognostic biomarker associated with immune infiltrates in gastric cancer

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12605
Author(s):  
Tongtong Zhang ◽  
Suyang Yu ◽  
Shipeng Zhao
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Survival Curve ◽  
Enrichment Analysis ◽  
Prognostic Indicator ◽  
Diagnostic Value ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Clinicopathological Parameters ◽  
The Relationship

Background Gastric cancer (GC) is the most prevalent malignancy among the digestive system tumors. Increasing evidence has revealed that lower mRNA expression of ANXA9 is associated with a poor prognosis in colorectal cancer. However, the role of ANXA9 in GC remains largely unknown. Material and Methods The Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas databases were used to investigate the expression of ANXA9 in GC, which was then validated in the four Gene Expression Omnibus (GEO) datasets. The diagnostic value of ANXA9 for GC patients was demonstrated using a receiver operating characteristic (ROC) curve. The correlation between ANXA9 expression and clinicopathological parameters was analyzed in The Cancer Genome Atlas (TCGA) and UALCAN databases. The Kaplan-Meier (K-M) survival curve was used to elucidate the relationship between ANXA9 expression and the survival time of GC patients. We then performed a gene set enrichment analysis (GSEA) to explore the biological functions of ANXA9. The relationship of ANXA9 expression and cancer immune infiltrates was analyzed using the Tumor Immune Estimation Resource (TIMER). In addition, the potential mechanism of ANXA9 in GC was investigated by analyzing its related genes. Results ANXA9 was significantly up-regulated in GC tissues and showed obvious diagnostic value. The expression of ANXA9 was related to the age, gender, grade, TP53 mutation, and histological subtype of GC patients. We also found that ANXA9 expression was associated with immune-related biological function. ANXA9 expression was also correlated with the infiltration level of CD8+ T cells, neutrophils, and dendritic cells in GC. Additionally, copy number variation (VNV) of ANXA9 occurred in GC patients. Function enrichment analyses revealed that ANXA9 plays a role in the GC progression by interacting with its related genes. Conclusions Our results provide strong evidence of ANXA9 expression as a prognostic indicator related to immune responses in GC.

Gene regulation through chromatin remodelling by members of the nuclear receptor superfamily

2000 ◽  
Vol 28 (4) ◽  
pp. 369-373 ◽  
Author(s):  
I. J. McEwan
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Transcription Factors ◽  
Thyroid Hormones ◽  
Target Gene ◽  
Protein Complexes ◽  
Nuclear Receptor Superfamily ◽  
Target Gene Expression ◽  
Dna Elements ◽  
Introductory Review

The intracellular receptors for steroid hormones, thyroid hormones, retinoids and vitamin D3 are known to bind to specific DNA elements and thus regulate target gene expression. This introductory review and the following papers address some of the mechanisms underlying this action. In particular, the ability of this family of transcription factors to recruit multi-protein complexes that have the capacity to remodel chromatin structure in order to silence or activate target gene expression is discussed.

scholarly journals Identification of Deregulated Transcription Factors Involved in Specific Bladder Cancer Subtypes

10.29007/v7qj ◽  
2020 ◽  
Author(s):  
Magali Champion ◽  
Julien Chiquet ◽  
Pierre Neuvial ◽  
Mohamed Elati ◽  
François Radvanyi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bladder Cancer ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Target Genes ◽  
The Cancer Genome Atlas ◽  
Reference Network ◽  
Data Set ◽  
Cancer Subtypes ◽  
Cancer Data

Comparison between tumoral and healthy cells may reveal abnormal regulation behaviors between a transcription factor and the genes it regulates, without exhibiting differential expression of the former genes. We propose a methodology for the identification of transcription factors involved in the deregulation of genes in tumoral cells. This strategy is based on the inference of a reference gene regulatory network that connects transcription factors to their downstream targets using gene expression data. Gene expression levels in tumor samples are then carefully compared to this reference network to detect deregulated target genes. A linear model is finally used to measure the ability of each transcription factor to explain these deregulations. We assess the performance of our method by numerical experiments on a public bladder cancer data set derived from the Cancer Genome Atlas project. We identify genes known for their implication in the development of specific bladder cancer subtypes as well as new potential biomarkers.

scholarly journals DNA accessibility is not the primary determinant of chromatin-mediated gene regulation

2019 ◽  
Author(s):  
Răzvan V. Chereji ◽  
Peter R. Eriksson ◽  
Josefina Ocampo ◽  
David J. Clark
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Transcription Factors ◽  
Restriction Enzyme ◽  
Chromatin Structure ◽  
Mouse Liver ◽  
Digestion Rate ◽  
Dna Accessibility ◽  
Primary Determinant ◽  
Liver Nuclei

ABSTRACTDNA accessibility is thought to be of major importance in regulating gene expression. We test this hypothesis using a restriction enzyme as a probe of chromatin structure and as a proxy for transcription factors. We measured the digestion rate and the fraction of accessible DNA at all genomicAluI sites in budding yeast and mouse liver nuclei. Hepatocyte DNA is more accessible than yeast DNA, consistent with longer linkers between nucleosomes, and indicating that nucleosome spacing is a major determinant of accessibility. DNA accessibility varies from cell to cell, such that essentially no sites are accessible or inaccessible in every cell.AluI sites in inactive mouse promoters are accessible in some cells, implying that transcription factors could bind without activating the gene. Euchromatin and heterochromatin have very similar accessibilities, suggesting that transcription factors can penetrate heterochromatin. Thus, DNA accessibility is not likely to be the primary determinant of gene regulation.

scholarly journals Endogenous BioID elucidates TCF7L1 interactome modulation upon GSK-3 inhibition in mouse ESCs

2018 ◽  
Author(s):  
Steven Moreira ◽  
Caleb Seo ◽  
Victor Gordon ◽  
Sansi Xing ◽  
Ruilin Wu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Transcription Factors ◽  
Target Gene ◽  
Single Copy ◽  
List Type ◽  
Interacting Proteins ◽  
Mouse Escs ◽  
Biotin Ligase ◽  
Biotin Labeling

Modulation of Wnt target gene expression via the TCF/LEFs remains poorly understood. We employ proximity-based biotin labeling (BioID) to examine GSK-3 inhibitor effects on the TCF7L1 interactome in mouse ESCs. We generated ESC lines with biotin ligase BirA* fused to TCF7L1 by knocking it into the endogenous TCF7L1 locus or by inserting a doxinducible BirA*-TCF7L1 transgene into the Rosa26 locus. Induction yielded BirA*-TCF7L1 levels 3-fold higher than in the endogenous system, but substantial overlap in biotinylated proteins with high peptide counts were detected by each method. Known TCF7L1 interactors TLE3/4 and β-catenin, and numerous proteins not previously associated with TCF7L1, were identified in both systems. Despite reduced BirA*-TCF7L1 levels, the number of hits identified with both BioID approaches increased after GSK-3 inhibition. We elucidate the network of TCF7L1 proximal proteins regulated by GSK-3 inhibition, validate the utility of endogenous BioID, and provide mechanistic insights into TCF7L1 target gene regulation.HighlightsBirA*-TCF7L1 at single-copy physiological levels generates robust BioID dataCHIR99021 reduces TCF7L1 levels but increases detectable TCF7L1-proximal proteinsThe TCF7L1 interactome of largely epigenetic/transcription factors fluctuates with GSK-3 inhibitionJMJD1C, SALL4 and BRG1/SMARCA4 are validated as TCF7L-interacting proteins

scholarly journals Identification and comparison of genes differentially regulated by transcription factors and miRNAs

2019 ◽  
Author(s):  
Amir Asiaee ◽  
Zachary B Abrams ◽  
Samantha Nakayiza ◽  
Deepa Sampath ◽  
Kevin R. Coombes
Keyword(s):  
Gene Regulation ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Linear Models ◽  
Critical Role ◽  
Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Coefficient Of Determination ◽  
Sequencing Data ◽  
Mirna Sequencing

AbstractTranscription factors and microRNAs (miRNA) both play a critical role in gene regulation and in the development of many diseases such as cancer. Understanding how transcription factors and miRNAs influence gene expression is thus important to understand, but complicated due to the large and interconnected nature of the human genome. To help better understand what genes are being regulated by transcription factors and/or miRNAs we looked at it over 8000 patient samples from 32 different cancer types collected from The Cancer Genome Atlas (TCGA). We started by clustering the transcription factors and miRNAs using Thresher to reduce the number of features. Using both the mRNA and miRNA sequencing data we constructed linear models to calculate the coefficient of determination (R2) for each mRNA based on the Thresher cluster expression. We generated three types of linear models: transcription factor, miRNA and transcription factor plus miRNA. We then determined genes that were highly explained or poorly explained by each of the three models based on the genes R2 value. We performed downstream gene enrichment analysis using ToppGene on the sets of well and poorly explained genes. This identified differences in gene regulation between transcription factors and miRNAs and showed what groups of gene are differentially regulated.

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