BRD4 promotes gastric cancer progression and metastasis through acetylation-dependent stabilization of Snail
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA554098 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9670800_1.fastq.gz | Fastqsanger.gz | |||
| SRR9670800_2.fastq.gz | Fastqsanger.gz | |||
| SRR9670792_1.fastq.gz | Fastqsanger.gz | |||
| SRR9670792_2.fastq.gz | Fastqsanger.gz | |||
| SRR9670793_1.fastq.gz | Fastqsanger.gz |
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Project description:The puropose of this study is to reveal a noncanonical post-transcriptional regulatory function of BRD4 that maintains cancer growth and dissemination, with immediate translational implication for treating metastatic malignancies with clinically available bromodomain inhibitors. The next-generation RNA sequencing was used to confirm the transcriptom overlapping change after BRD4 and Snail knockout separately.
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Project description:Epithelial-mesenchymal transition (EMT) is in the highlights as a significant role in tumor progression and invasion. Snail was known as the one of regulators of EMT in various malignant tumors. The aim of this study was to investigate the effect of Snail on invasiveness/migratory ability of gastric cancer cell lines and clinicopathological and prognostic significance of Snail over-expression using immunohistochemistry in tissue microarray of 314 gastric adenocarcinomas (GC). Differential gene expression in Snail over-expressed GC was investigated using cDNA microarray analysis. Silencing of Snail by ShRNA induced decreased of invasion, migration of gastric cancer cell lines. In contrast, over-expression of Snail induced increased invasiveness and migratory ability of gastric cancer cell lines in accordance increase of VEGF and MMP11. Furthermore, the over-expression of Snail (≥75% nuclear staining of Snail) was significantly associated with tumor progression (p<0.0001), lymph node metastases (p=0.002), lymphovascular invasion (p=0.002), and perineural invasion (p=0.002) in 314 GC patient. Snail over-expression was also associated with poor prognosis (shorter survival) in GC patients (p=0.023). cDNA microarray revealed 213 differential expressed genes in Snail over-expressed GC tissues, including genes related to metastasis, invasion. Based on above results, it was suggested that Snail plays a significant role in invasiveness/migratory ability of GCs. In addition, Snail might be used to predictive biomarker for evaluation of prognosis or aggressiveness in GCs.
2012-05-18 | GSE38024 | GEO
Project description:Epithelial-mesenchymal transition (EMT) is in the highlights as a significant role in tumor progression and invasion. Snail was known as the one of regulators of EMT in various malignant tumors. The aim of this study was to investigate the effect of Snail on invasiveness/migratory ability of gastric cancer cell lines and clinicopathological and prognostic significance of Snail over-expression using immunohistochemistry in tissue microarray of 314 gastric adenocarcinomas (GC). Differential gene expression in Snail over-expressed GC was investigated using cDNA microarray analysis. Silencing of Snail by ShRNA induced decreased of invasion, migration of gastric cancer cell lines. In contrast, over-expression of Snail induced increased invasiveness and migratory ability of gastric cancer cell lines in accordance increase of VEGF and MMP11. Furthermore, the over-expression of Snail (?75% nuclear staining of Snail) was significantly associated with tumor progression (p<0.0001), lymph node metastases (p=0.002), lymphovascular invasion (p=0.002), and perineural invasion (p=0.002) in 314 GC patient. Snail over-expression was also associated with poor prognosis (shorter survival) in GC patients (p=0.023). cDNA microarray revealed 213 differential expressed genes in Snail over-expressed GC tissues, including genes related to metastasis, invasion. Based on above results, it was suggested that Snail plays a significant role in invasiveness/migratory ability of GCs. In addition, Snail might be used to predictive biomarker for evaluation of prognosis or aggressiveness in GCs. 48 primary gastric adenocarcinoma fresh frozen tissues were used for microarray. All the tissues were obtained after curative resection after pathologic confirm at Pusan National University Hospital (PNUH, Busan, Korea) and Cheonnam University Hospital (CNUH, Cheonnam, Korea). Microarray experiment and data analysis were done at Cancer research institute, PNUH, Busan, Korea.
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Project description:In addition to acetylation, histones are modified by a series of competing longer chain acylations. Most of these acylation marks are enriched and co-exist with acetylation on active gene regulatory elements. Their seemingly redundant functions have hindered the understanding of histone acylations’ specific roles. Here, by using an acute lymphoblastic leukaemia (ALL) cell model and blasts from B-ALL patients, we demonstrate a role for mitochondrial activity in controlling histone acylation/acetylation ratio, especially at H4K5. An increase of the crotonylation and butyrylation over acetylation on H4K5 weakens BRD4-chromatin interaction and increases BRD4 nuclear mobility and availability for binding transcription start site associated nucleosome free regions of active genes. Our data suggest that, with regard to BRD4 dynamics, histone acylations including acetylation, should be considered collectively. A metabolism dependant control of the histone acetylation/longer chain acylation(s) ratio could constitute a common mechanism regulating bromodomain factors’ “reservoir” pool, availability and functional genomic distribution.
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Project description:In addition to acetylation, histones are modified by a series of competing longer chain acylations. Most of these acylation marks are enriched and co-exist with acetylation on active gene regulatory elements. Their seemingly redundant functions have hindered the understanding of histone acylations’ specific roles. Here, by using an acute lymphoblastic leukaemia (ALL) cell model and blasts from B-ALL patients, we demonstrate a role for mitochondrial activity in controlling histone acylation/acetylation ratio, especially at H4K5. An increase of the crotonylation and butyrylation over acetylation on H4K5 weakens BRD4-chromatin interaction and increases BRD4 nuclear mobility and availability for binding transcription start site associated nucleosome free regions of active genes. Our data suggest that, with regard to BRD4 dynamics, histone acylations including acetylation, should be considered collectively. A metabolism dependant control of the histone acetylation/longer chain acylation(s) ratio could constitute a common mechanism regulating bromodomain factors’ “reservoir” pool, availability and functional genomic distribution.
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Project description:In addition to acetylation, histones are modified by a series of competing longer chain acylations. Most of these acylation marks are enriched and co-exist with acetylation on active gene regulatory elements. Their seemingly redundant functions have hindered the understanding of histone acylations’ specific roles. Here, by using an acute lymphoblastic leukaemia (ALL) cell model and blasts from B-ALL patients, we demonstrate a role for mitochondrial activity in controlling histone acylation/acetylation ratio, especially at H4K5. An increase of the crotonylation and butyrylation over acetylation on H4K5 weakens BRD4-chromatin interaction and increases BRD4 nuclear mobility and availability for binding transcription start site associated nucleosome free regions of active genes. Our data suggest that, with regard to BRD4 dynamics, histone acylations including acetylation, should be considered collectively. A metabolism dependant control of the histone acetylation/longer chain acylation(s) ratio could constitute a common mechanism regulating bromodomain factors’ “reservoir” pool, availability and functional genomic distribution.
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Project description:In addition to acetylation, histones are modified by a series of competing longer chain acylations. Most of these acylation marks are enriched and co-exist with acetylation on active gene regulatory elements. Their seemingly redundant functions have hindered the understanding of histone acylations’ specific roles. Here, by using an acute lymphoblastic leukaemia (ALL) cell model and blasts from B-ALL patients, we demonstrate a role for mitochondrial activity in controlling histone acylation/acetylation ratio, especially at H4K5. An increase of the crotonylation and butyrylation over acetylation on H4K5 weakens BRD4-chromatin interaction and increases BRD4 nuclear mobility and availability for binding transcription start site associated nucleosome free regions of active genes. Our data suggest that, with regard to BRD4 dynamics, histone acylations including acetylation, should be considered collectively. A metabolism dependant control of the histone acetylation/longer chain acylation(s) ratio could constitute a common mechanism regulating bromodomain factors’ “reservoir” pool, availability and functional genomic distribution.
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Project description:In addition to acetylation, histones are modified by a series of competing longer chain acylations. Most of these acylation marks are enriched and co-exist with acetylation on active gene regulatory elements. Their seemingly redundant functions have hindered the understanding of histone acylations’ specific roles. Here, by using an acute lymphoblastic leukaemia (ALL) cell model and blasts from B-ALL patients, we demonstrate a role for mitochondrial activity in controlling histone acylation/acetylation ratio, especially at H4K5. An increase of the crotonylation and butyrylation over acetylation on H4K5 weakens BRD4-chromatin interaction and increases BRD4 nuclear mobility and availability for binding transcription start site associated nucleosome free regions of active genes. Our data suggest that, with regard to BRD4 dynamics, histone acylations including acetylation, should be considered collectively. A metabolism dependant control of the histone acetylation/longer chain acylation(s) ratio could constitute a common mechanism regulating bromodomain factors’ “reservoir” pool, availability and functional genomic distribution.
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Project description:In addition to acetylation, histones are modified by a series of competing longer chain acylations. Most of these acylation marks are enriched and co-exist with acetylation on active gene regulatory elements. Their seemingly redundant functions have hindered the understanding of histone acylations’ specific roles. Here, by using an acute lymphoblastic leukaemia (ALL) cell model and blasts from B-ALL patients, we demonstrate a role for mitochondrial activity in controlling histone acylation/acetylation ratio, especially at H4K5. An increase of the crotonylation and butyrylation over acetylation on H4K5 weakens BRD4-chromatin interaction and increases BRD4 nuclear mobility and availability for binding transcription start site associated nucleosome free regions of active genes. Our data suggest that, with regard to BRD4 dynamics, histone acylations including acetylation, should be considered collectively. A metabolism dependant control of the histone acetylation/longer chain acylation(s) ratio could constitute a common mechanism regulating bromodomain factors’ “reservoir” pool, availability and functional genomic distribution.
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