Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA273658 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1772973.fastq.gz | Fastqsanger.gz | |||
| SRR1772974.fastq.gz | Fastqsanger.gz | |||
| SRR1772975.fastq.gz | Fastqsanger.gz |
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Project description:The transcription factor RUNX1 exhibits recurrent loss-of-function mutations in estrogen receptor-positive (ER+) breast cancer (BCa). Its knockdown in vitro decreased AXIN1 expression in estrogen-dependent manner. Consistently, RUNX1 and AXIN1 mRNA levels are strongly correlated in ER+, not ER- tumors. RUNX1 occupies AXIN1â??s second intron in living cells, abutting an ERa-binding site. Potentially promoting BCa progression, decreased AXIN1 expression after RUNX1 knockdown associated with upregulation of b-catenin, and this was preventable by AXIN stabilizers. Unlike in colon cancer, however, deregulation of b-catenin in BCa cells affect neither c-Myc, nor CCND1, nor G1/S cell cycle phase transition. Instead, cyclin B1 was decreased and the G2/M checkpoint was compromised as indicated by mitotic slippage in the presence of microtubule disruptors. Thus, combined analysis of the RUNX1 transcriptome, its cistrome, and differential mRNA expression in tumors with wild type versus mutant RUNX1, altogether highlight a role for the RUNX1/AXIN1/b-catenin axis in ER+ BCa. Significance: Three recent exome sequencing studies assigned to RUNX1 a BCa suppressor role. The present study begins to uncover the underlying molecular mechanisms, offers an explanation for the specificity to ER+ tumors, and marks AXIN1 as a therapeutic target for ER+/RUNX1- BCa. Examination of RUNX1 binding in MCF7 cells
2016-02-22 | E-GEOD-65313 | biostudies-arrayexpress
Project description:The transcription factor RUNX1 exhibits recurrent loss-of-function mutations in estrogen receptor-positive (ER+) breast cancer (BCa). Its knockdown in vitro decreased AXIN1 expression in estrogen-dependent manner. Consistently, RUNX1 and AXIN1 mRNA levels are strongly correlated in ER+, not ER- tumors. RUNX1 occupies AXIN1’s second intron in living cells, abutting an ERa-binding site. Potentially promoting BCa progression, decreased AXIN1 expression after RUNX1 knockdown associated with upregulation of b-catenin, and this was preventable by AXIN stabilizers. Unlike in colon cancer, however, deregulation of b-catenin in BCa cells affect neither c-Myc, nor CCND1, nor G1/S cell cycle phase transition. Instead, cyclin B1 was decreased and the G2/M checkpoint was compromised as indicated by mitotic slippage in the presence of microtubule disruptors. Thus, combined analysis of the RUNX1 transcriptome, its cistrome, and differential mRNA expression in tumors with wild type versus mutant RUNX1, altogether highlight a role for the RUNX1/AXIN1/b-catenin axis in ER+ BCa. Significance: Three recent exome sequencing studies assigned to RUNX1 a BCa suppressor role. The present study begins to uncover the underlying molecular mechanisms, offers an explanation for the specificity to ER+ tumors, and marks AXIN1 as a therapeutic target for ER+/RUNX1- BCa.
2016-02-22 | GSE65313 | GEO
Project description:RUNX1 is a transcription factor functioning both as an oncogene and a tumor suppressor in breast cancer. RUNX1 alters chromatin structure in cooperation with chromatin modifier and remodeling enzymes. In this study, we examined the relationship between RUNX1-mediated transcription and genome organization. We characterized genome-wide RUNX1 localization and performed RNA-seq and Hi-C in RUNX1-depleted and control MCF-7 breast cancer cells. RNA-seq analysis showed that RUNX1 depletion led to up-regulation of genes associated with chromatin structure and down-regulation of genes related to extracellular matrix biology, as well as NEAT1 and MALAT1 lncRNAs. Our ChIP-Seq analysis supports a prominent role for RUNX1 in transcriptional activation. About 30% of all RUNX1 binding sites were intergenic, indicating diverse roles in promoter and enhancer regulation and suggesting additional functions for RUNX1. Hi-C analysis of RUNX1-depleted cells demonstrated that overall three-dimensional genome organization is largely intact, but indicated enhanced association of RUNX1 near Topologically Associating Domain (TAD) boundaries and alterations in long-range interactions. These results suggest an architectural role for RUNX1 in fine-tuning local interactions rather than in global organization. Our results provide novel insight into RUNX1-mediated perturbations of higher-order genome organization that are functionally linked with RUNX1-dependent compromised gene expression in breast cancer cells. Hi-C and RNA-seq experiments were conducted in MCF-7 shNS and shRUNX1 cells. RUNX1 ChIP-seq was conducted in wildtype MCF-7 cells.
2016-08-23 | E-GEOD-75070 | biostudies-arrayexpress
Project description:RUNX1 is a transcription factor functioning both as an oncogene and a tumor suppressor in breast cancer. RUNX1 alters chromatin structure in cooperation with chromatin modifier and remodeling enzymes. In this study, we examined the relationship between RUNX1-mediated transcription and genome organization. We characterized genome-wide RUNX1 localization and performed RNA-seq and Hi-C in RUNX1-depleted and control MCF-7 breast cancer cells. RNA-seq analysis showed that RUNX1 depletion led to up-regulation of genes associated with chromatin structure and down-regulation of genes related to extracellular matrix biology, as well as NEAT1 and MALAT1 lncRNAs. Our ChIP-Seq analysis supports a prominent role for RUNX1 in transcriptional activation. About 30% of all RUNX1 binding sites were intergenic, indicating diverse roles in promoter and enhancer regulation and suggesting additional functions for RUNX1. Hi-C analysis of RUNX1-depleted cells demonstrated that overall three-dimensional genome organization is largely intact, but indicated enhanced association of RUNX1 near Topologically Associating Domain (TAD) boundaries and alterations in long-range interactions. These results suggest an architectural role for RUNX1 in fine-tuning local interactions rather than in global organization. Our results provide novel insight into RUNX1-mediated perturbations of higher-order genome organization that are functionally linked with RUNX1-dependent compromised gene expression in breast cancer cells.
2016-08-23 | GSE75070 | GEO
Project description:The nuclear receptor, estrogen receptor alpha (ERα), controls the expression of hundreds of genes responsible for target cell phenotypic properties, but the relative importance of direct vs. tethering mechanisms of DNA binding has not been established. In this first report, we examine the genome-wide chromatin localization of an altered-specificity mutant ER with a DNA-binding domain deficient in binding to estrogen response element (ERE)-containing DNA (DBDmut ER) vs. wild type ERα. Using high-throughput sequencing of ER chromatin immunoprecipitations (ChIP-Seq) and mRNA transcriptional profiling, we show that direct ERE binding is required for most (75%) estrogen-dependent gene regulation and 90% of hormone-dependent recruitment of ER to genomic binding sites. De novo motif analysis of the chromatin binding regions in MDA-MB-231 human breast cancer cells defined unique transcription factor profiles responsible for genes regulated through tethering vs. direct DNA (ERE) binding, with Runx motifs enriched in ER-tethered sites. We confirmed a role for Runx1 in mediating ERa genomic recruitment and regulation of tethering genes. Our findings delineate the contributions of ERE binding vs. binding through response elements for other transcription factors in chromatin localization and ER-dependent gene regulation, paradigms likely to underlie the gene regulatory actions of other nuclear receptors as well. This SuperSeries is composed of the following subset Series: GSE22593: WT and DBDmut Breast Cancer Cells GSE22609: Genome-Wide Maps of WT and DBDmut Estrogen Receptor in Human Breast Cancer Cells Refer to individual Series
2010-06-29 | E-GEOD-22610 | biostudies-arrayexpress
Project description:Previous studies have identified an interaction between RUNX1 and estrogen receptor alpha and its potential role in estrogen signaling in breast cancer. To determine the transcriptomic actions of RUNX1, we knocked down its expression by using siRNAs, both in the absence and presence of estradiol (E2).
2022-06-01 | GSE115475 | GEO
Project description:Gene expression analysis of MEL-18-silenced MCF7 cell lines. MEL-18 is a component of the polycomb repressive complex (PRC)-1, which is a critical epigenetic modulator of stem cell regulation and normal and cancerous development. Accumulating studies have suggested that MEL-18 might act as a tumor suppressor in several human tumors, including breast cancer. Results provide insight into the functional role of MEL-18 in estrogen-dependent breast cancer.
2015-05-01 | GSE64716 | GEO
Project description:Aberrant activation of Wnt/β-catenin signaling is observed in numerous cancers. In hepatocellular carcinoma activating mutations in CTNNB1 (20-25%) or loss of function mutations in AXIN1 (10%), AXIN2 (2%) and APC (1-2%) are observed. All these mutations lead to aberrant stabilization of β-catenin, which constitutively activates downstream Wnt/β-catenin target genes and triggers a genetic program resulting in tumor formation. However, in relation to AXIN1 mutations some reports have challenged whether these indeed result in tumor growth by enhancing β-catenin signaling (e.g. PMID: 16964294, 29525529). Several alternative pathways have also been linked to AXIN1 (ENSG00000103126), such as TGFβ, SAPK/JNK, p53, YAP/TAZ and c-myc. To identify which one of these or other unknown signaling routes are linked to AXIN1, using CRISPR-Cas9 genome editing, we have successfully repaired the homozygous p.R712* AXIN1 mutation present in the SNU449 hepatocellular carcinoma cell line. Next, using RNA sequencing the RNA expression patterns of 3 independent repaired clones were compared with 3 clones retaining the AXIN1 mutation. Surprisingly, only 5 genes were significantly altered in the repaired clones, among which AXIN2, a well-established β-catenin target gene. Thus, this analysis leads to the surprising observation that a commonly observed mutation in a hepatocellular tumor suppressor gene, is associated with minimal alterations in gene expression, at least in the SNU449 cell line.
2019-01-01 | GSE119001 | GEO
Project description:Breast cancer is one of the most prevalent cancers in women worldwide. Through the regulation of many coding and non-coding target genes, estrogen (E2 or 17b-estradiol) and its nuclear receptor ERα play important roles in breast cancer development and progression. Despite intensive studies on estrogen-regulated coding genes over the past decades, molecular mechanisms underlying estrogen-regulated non-coding RNAs in breast cancer remain to be elucidated. Here, we performed extensive epigenomic studies including GRO-seq and ATAC-seq, and identified genome-wide estrogen-regulated long non-coding RNAs (lncRNAs). Similar to the coding targets of ERα, the transcription of estrogen-regulated lncRNAs correlates with the activation status of ERα-bound enhancers, measured by eRNA production, chromatin accessibility, and the occupancy of the enhancer regulatory components including P300, MED1, and ARID1B. Our 3D chromatin architecture analyses suggest that lncRNAs and their neighboring E2-resonsive coding genes, exemplified by LINC00160 and RUNX1, might be regulated as a 3D structural unit resulted from enhancer-promoter interactions. Finally, we evaluated the expression levels of LINC00160 and RUNX1 in various types of breast cancer and found that their expression positively correlated with the survival rate in ER+ breast cancer patients, implying that the estrogen-regulated LINC00160 and its neighboring RUNX1 might represent potential biomarkers for ER+ breast cancers.
2020-09-30 | GSE144925 | GEO
Project description:Breast cancer is one of the most prevalent cancers in women worldwide. Through the regulation of many coding and non-coding target genes, estrogen (E2 or 17b-estradiol) and its nuclear receptor ERα play important roles in breast cancer development and progression. Despite intensive studies on estrogen-regulated coding genes over the past decades, molecular mechanisms underlying estrogen-regulated non-coding RNAs in breast cancer remain to be elucidated. Here, we performed extensive epigenomic studies including GRO-seq and ATAC-seq, and identified genome-wide estrogen-regulated long non-coding RNAs (lncRNAs). Similar to the coding targets of ERα, the transcription of estrogen-regulated lncRNAs correlates with the activation status of ERα-bound enhancers, measured by eRNA production, chromatin accessibility, and the occupancy of the enhancer regulatory components including P300, MED1, and ARID1B. Our 3D chromatin architecture analyses suggest that lncRNAs and their neighboring E2-resonsive coding genes, exemplified by LINC00160 and RUNX1, might be regulated as a 3D structural unit resulted from enhancer-promoter interactions. Finally, we evaluated the expression levels of LINC00160 and RUNX1 in various types of breast cancer and found that their expression positively correlated with the survival rate in ER+ breast cancer patients, implying that the estrogen-regulated LINC00160 and its neighboring RUNX1 might represent potential biomarkers for ER+ breast cancers.
2020-09-30 | GSE144926 | GEO