Journal: Cells

Article Title: Anti-microRNA-21 Therapy on Top of ACE Inhibition Delays Renal Failure in Alport Syndrome Mouse Models

doi: 10.3390/cells11040594

Figure Lengend Snippet: Member gene expression profiles from the MetaBase pathway “Renal tubulointerstitial injury in lupus nephritis” (curated by Clarivate Analytics). The Y axis represents Log2(FPKM + 1) values in each of the four animal groups and the genes on the X axis are ordered by their mean expression values in the vehicle-treated F1- Col4a3 −/− group.

Article Snippet: MetaBase pathway gene sets (July 2018 version) were extracted with the metabaser R package (version 4.3.0), available through Sanofi-Genzyme’s subscription to the CBDD (Computational Biology Methods for Drug Discovery) program (Clarivate Analytics).

Techniques: Gene Expression, Expressing

Journal: Cells

Article Title: Anti-microRNA-21 Therapy on Top of ACE Inhibition Delays Renal Failure in Alport Syndrome Mouse Models

doi: 10.3390/cells11040594

Figure Lengend Snippet: Member gene expression profiles from the MetaBase pathway “Mitochondrial dysfunction in neurodegenerative diseases” (curated by Clarivate Analytics), with the same plotting parameters as in .

Article Snippet: MetaBase pathway gene sets (July 2018 version) were extracted with the metabaser R package (version 4.3.0), available through Sanofi-Genzyme’s subscription to the CBDD (Computational Biology Methods for Drug Discovery) program (Clarivate Analytics).

Techniques: Gene Expression

Journal: Journal of Cell Communication and Signaling

Article Title: YY1 regulated transcription‐based stratification of gastric tumors and identification of potential therapeutic candidates

doi: 10.1007/s12079-021-00608-4

Figure Lengend Snippet: Identification of YY1 regulated genes in gastric cancer cells. a RNAi mediated silencing of YY1 gene in AGS cells results in the decreased CBF/YY1/NFYA reporter activity. Graph shows YY1-mediated reporter activity measured by dual luciferase assay at 36 h after the transfection of YY1 siRNA. b YY1 gene silencing in AGS cells also results in the reduced mRNA expression of YY1 gene. In the semi-quantiative RT-PCR, expression of GADPH serves as internal control. c RNAi mediated silencing of YY1 gene in AGS cells results in the inhibition of multiple oncogenic signaling pathways including CBF/NFYA/YY1, JNK/MAPK, ERK/MAPK, HIF, Wnt, and ER as measured by dual luciferase assay. d Genome-wide mRNA profiling was performed in AGS cells, upon silencing YY1, using Affymetrix GeneChip Human Transcriptome Array 2.0 (HTA 2.0). Heatmap depicts upregulated and downregulated genes with fold change cut off > 1.5 and <-1.5 upon YY1 silencing. In the specified cut off, 459 genes are upregulated and 233 genes are downregulated. e–f Analysis of the transcription factor binding sites among the genes upregulated (e) and downregulated (f) upon YY1 silencing using DiRE transcription factor analysis tool. Analysis shows the predominant occurrence of GFI1, HOXA4, OCT-1, GATA2, YY1, TAL1 and others

Article Snippet: YY1 pathway specific gene sets GCCATNTTG_YY1_Q6 (Xie et al. 2005 ), YY1_01, YY1_02 and YY1_Q6 (Xiaohui Xie, Broad Institute), DE_YY1_TARGETS_UP and DE_YY1_TARGETS_DN (de Nigris et al. 2008 ) were collected from molecular signatures database (MSigDB) (Liberzon et al. 2011 ).

Techniques: Activity Assay, Luciferase, Transfection, Expressing, Reverse Transcription Polymerase Chain Reaction, Control, Inhibition, Protein-Protein interactions, Genome Wide, Binding Assay

Journal: Journal of Cell Communication and Signaling

Article Title: YY1 regulated transcription‐based stratification of gastric tumors and identification of potential therapeutic candidates

doi: 10.1007/s12079-021-00608-4

Figure Lengend Snippet: The YY1 gene sets show moderate overlap among them. a List of YY1 gene sets from molecular signatures database and GEO datasets used in the study. b The genes occur in different YY1 gene sets show moderate overlap. Eleven different YY1 gene sets show poor overlap and this shows the different sets of genes associated with YY1 in different biological conditions. Few of the YY1 motif gene sets show a considerable overlap among them. c The eleven YY1 gene sets were analyzed for their possible regulation based on the occurrence of transcription factor binding sites. The overlap analysis among the top 20 transcription factors occur across eleven YY1 gene sets reveal the occurrence of binding sites for YY1, NFMUE1, OCT-1, WT1, CREB, STAT6, CDP, E2F, RFX1, ZNF219, E2, TTF1, SRY, MOVOB, TST1, VDR, GATA2 and NCX

Article Snippet: YY1 pathway specific gene sets GCCATNTTG_YY1_Q6 (Xie et al. 2005 ), YY1_01, YY1_02 and YY1_Q6 (Xiaohui Xie, Broad Institute), DE_YY1_TARGETS_UP and DE_YY1_TARGETS_DN (de Nigris et al. 2008 ) were collected from molecular signatures database (MSigDB) (Liberzon et al. 2011 ).

Techniques: Binding Assay

Journal: Journal of Cell Communication and Signaling

Article Title: YY1 regulated transcription‐based stratification of gastric tumors and identification of potential therapeutic candidates

doi: 10.1007/s12079-021-00608-4

Figure Lengend Snippet: Differential activation pattern of YY1 gene sets across the subtypes of gastric tumors. Gene signature-based pathway activation analysis was performed for different YY1 gene sets across the mRNA profile GSE15459 with 200 gastric tumors. a The activation pattern of YY1 gene sets across gastric tumors reveal that YY1 gene sets to highly express in intestinal subtype gastric tumors. b AGS_YY1_siRNA_UP and AGS_YY1_siRNA_DN gene sets are activated in majority of intestinal subtype gastric tumors and a subset of diffuse subtype gastric tumors. c The gene sets representing those positively regulated by YY1 (down gene sets) show higher expression in intestinal subtype gastric tumors. This shows that YY1 gene sets are expressed in a major subset of intestinal subtype gastric tumors

Article Snippet: YY1 pathway specific gene sets GCCATNTTG_YY1_Q6 (Xie et al. 2005 ), YY1_01, YY1_02 and YY1_Q6 (Xiaohui Xie, Broad Institute), DE_YY1_TARGETS_UP and DE_YY1_TARGETS_DN (de Nigris et al. 2008 ) were collected from molecular signatures database (MSigDB) (Liberzon et al. 2011 ).

Techniques: Activation Assay, Expressing

Journal: Journal of Cell Communication and Signaling

Article Title: YY1 regulated transcription‐based stratification of gastric tumors and identification of potential therapeutic candidates

doi: 10.1007/s12079-021-00608-4

Figure Lengend Snippet: YY1 correlated gene sets show elevated expression in intestinal subtype gastric tumors. a The 64 genes in the YY1 gene sets were derived by probing the genes with high correlation in terms of expression pattern with the activation pattern of other YY1 gene sets across gastric tumors in the profile GSE15459. The 30, YY1-correlated genes showed the predominant activation in intestinal subtype gastric tumors. b–d Gene set enrichment analysis of YY1 correlated genes in gastric tumor datasets GSE15459 (b), GSE35809 (c) and GSE62254 (d) reveal their elevated expression in intestinal subtype gastric tumors

Article Snippet: YY1 pathway specific gene sets GCCATNTTG_YY1_Q6 (Xie et al. 2005 ), YY1_01, YY1_02 and YY1_Q6 (Xiaohui Xie, Broad Institute), DE_YY1_TARGETS_UP and DE_YY1_TARGETS_DN (de Nigris et al. 2008 ) were collected from molecular signatures database (MSigDB) (Liberzon et al. 2011 ).

Techniques: Expressing, Derivative Assay, Activation Assay

Journal: Journal of Cell Communication and Signaling

Article Title: YY1 regulated transcription‐based stratification of gastric tumors and identification of potential therapeutic candidates

doi: 10.1007/s12079-021-00608-4

Figure Lengend Snippet: Analysis of YY1 associated pathways in gastric tumors. Gene set based pathway activation scoring of YY1 gene sets with 189 oncogenic signatures from Molecular Signatures Database (MSigDB) across the 200 samples in the in gastric tumor mRNA profile GSE15459. AGS_YY1_siRNA_DN signature shows association with β-catenin, AKT and Cyclin-D1 gene sets, with higher expression in a major subset of intestinal subtype and a subset of diffuse subtype gastric tumors. The AGS_YY1_siRNA_UP gene set shows association with Myc, E2F, MTOR, PDGF and VEGF pathways

Article Snippet: YY1 pathway specific gene sets GCCATNTTG_YY1_Q6 (Xie et al. 2005 ), YY1_01, YY1_02 and YY1_Q6 (Xiaohui Xie, Broad Institute), DE_YY1_TARGETS_UP and DE_YY1_TARGETS_DN (de Nigris et al. 2008 ) were collected from molecular signatures database (MSigDB) (Liberzon et al. 2011 ).

Techniques: Activation Assay, Expressing

Journal: Journal of Cell Communication and Signaling

Article Title: YY1 regulated transcription‐based stratification of gastric tumors and identification of potential therapeutic candidates

doi: 10.1007/s12079-021-00608-4

Figure Lengend Snippet: Identification of drugs showing negative correlation with the expression of YY1 gene sets. a, b Correlation analysis between the expression of YY1 gene set and IC50 of 320 drugs in the Genomics of Drug Sensitivity in Cancer dataset-1 (GDSC1) was performed across 23 gastric cancer cell lines. The top ten drugs with high negative score are shown. Full list is provided in Supplementary Table 4. a The top panel shows the expression pattern of YY1 gene sets across gastric cancer cell lines and b the lower panel shows the IC50 of selected 10 drugs across the gastric cancer cell lines in the same order. A negative correlation between the expression pattern of YY1 gene set and the sensitivity of drugs is notable. c, d Similar trend of negative correlation between YY1 gene sets and a panel of drugs in Cancer Cell Line Encyclopedia (CCLE) database. The complete list is provided in Supplementary Table 6. e The connectivity map analysis for 152 YY1 genes show the drugs with negative tau score to be associated with YY1 gene set. Notably, many of the top hit drugs with negative association to be the HDAC inhibitors

Article Snippet: YY1 pathway specific gene sets GCCATNTTG_YY1_Q6 (Xie et al. 2005 ), YY1_01, YY1_02 and YY1_Q6 (Xiaohui Xie, Broad Institute), DE_YY1_TARGETS_UP and DE_YY1_TARGETS_DN (de Nigris et al. 2008 ) were collected from molecular signatures database (MSigDB) (Liberzon et al. 2011 ).

Techniques: Expressing

Journal: Journal of Cell Communication and Signaling

Article Title: YY1 regulated transcription‐based stratification of gastric tumors and identification of potential therapeutic candidates

doi: 10.1007/s12079-021-00608-4

Figure Lengend Snippet: In vitro validation of drugs predicted to inhibit the expression of YY1-regulated genes in gastric cancer cells. Selected drugs predicted to have negative correlation in terms of IC50 and expression of YY1 gene set across GDSC1, GDSC2, CCLE and NCI60 datasets were validated for their in vitro feature of inhibiting YY1-regulated transcription in stable YY1 firefly luciferase reporter AGS-YY1-Fluc cells by firefly luciferase assay. Wee1 Inhibitor (a), roscovitine (b), dastinib (c), paclitaxel (d), erlotinib (e), camptothecin (f), tamoxifen (g), atorvastatin (h), 5-Fluorouracil (i), cyclophosphamide (j), doxorubicin (k), mitoxantrone (l), vinblastine (m) and irinotecan (n) treatment at both 1 µM and 5 µM concentrations in AGS-YY1-Fluc cells at 36 h of drug treatment show the inhibition of YY1 reporter activity as assessed by firefly luciferase reporter assay. This shows the suitability of these drugs for inhibiting YY1 regulated transcription in gastric cancer cells

Article Snippet: YY1 pathway specific gene sets GCCATNTTG_YY1_Q6 (Xie et al. 2005 ), YY1_01, YY1_02 and YY1_Q6 (Xiaohui Xie, Broad Institute), DE_YY1_TARGETS_UP and DE_YY1_TARGETS_DN (de Nigris et al. 2008 ) were collected from molecular signatures database (MSigDB) (Liberzon et al. 2011 ).

Techniques: In Vitro, Biomarker Discovery, Expressing, Luciferase, Inhibition, Activity Assay, Reporter Assay