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Exosome-mediated interaction in the tumor microenvironment modulates MIR211 response via the DUSP6-ERK5 axis and contributes to BRAFV600E inhibitor resistance in melanoma

ABSTRACT: Exosome-mediated interaction in the tumor microenvironment modulates MIR211 response via the DUSP6-ERK5 axis and contributes to BRAFV600E inhibitor resistance in melanoma

PROVIDER: PRJNA517675 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8502860.fastq.gz	Fastqsanger.gz
	SRR8502870.fastq.gz	Fastqsanger.gz
	SRR8502861.fastq.gz	Fastqsanger.gz
	SRR8502871.fastq.gz	Fastqsanger.gz
	SRR8502862.fastq.gz	Fastqsanger.gz

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Exosome-mediated interaction in the tumor microenvironment modulates MIR211 response via the DUSP6-ERK5 axis and contributes to BRAFV600E inhibitor resistance in melanoma

Project description:It is uncertain whether the microRNA MIR211 is a tumor suppressor or an oncogene. To resolve this, we ectopically expressed MIR211 in BRAFV600E-mutant A375 melanoma cells and examined its effect in mouse xenografts. Ectopic MIR211 expression promoted aggressive tumor growth accompanied by increased cellular proliferation and angiogenesis. We provide evidence that MIR211 transfers to adjacent mouse endothelial cells via exosomes and alter the cellular properties. Cross-species transcriptomic analysis showed that human tumor-derived MIR211 interacts with the mouse transcriptome and activates ERK5 signaling in tumor cells via modulation of a feedback loop. MIR211 directly inhibited the DUSP6 protein phosphatase, a novel MIR211 target, as confirmed by RNA immunopurification with RNA-seq and target cleavage assays. Finally, MIR211 expression conferred resistance to the BRAF inhibitor vemurafenib and the MEK inhibitor cobimetinib, with associated increases in ERK5 phosphorylation. These findings are consistent with a model in which MIR211 regulates melanoma tumor proliferation and BRAF inhibitor resistance by inducing ERK5 signaling within the complex tumor microenvironment. We propose that the MIR211-ERK5 axis represents an important and sensitive regulatory arm in melanoma with potential theranostic applications.

2021-01-29 | GSE125836 | GEO

Gene expression data of BCR-ABL1 transformed B cell precursors from Dusp6 wild-type and Dusp6 knockout mice

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Phospho-proteomic analysis of DUSP6 deficient Caco-2 cells

Project description:Dual-specificity phosphatase 6 (Dusp6)-deficiency enhances baseline colon barrier integrity and confers amelioration of dextran sulfate sodium (DSS)-induced colonic injury. DUSP6 is a phosphatase, and therefore it is plausible that DUSP6 knockout alters the phosphorylation status of other proteins. To access the protein phosphorylation landscape and functional network in DUSP6 deficient Caco-2 cells, we applied phosphopeptide enrichment and isobaric labeling strategies with MS-based proteomics, and identified 1323 phosphorylation sites on 580 phosphoproteins.

2021-11-02 | PXD029014 | Pride

Gene expression data of BCR-ABL1 transformed B cell precursors from Dusp6 wild-type and Dusp6 knockout mice

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The RNA exosome contributes to gene expression regulation during stem cell differentiation [CAGE]

Project description:Gene expression programs change during cellular transitions. It is well established that a network of transcription factors and chromatin modifiers regulate RNA levels during embryonic stem cell (ESC) differentiation, but the full impact of post-transcriptional processes remains elusive. While cytoplasmic RNA turnover mechanisms have been implicated in differentiation, the contribution of nuclear RNA decay has not been investigated. Here, we differentiate mouse ESCs, depleted for the ribonucleolytic RNA exosome, into embryoid bodies to determine to which degree RNA abundance in the two states can be attributed to changes in transcription vs. RNA decay by the exosome. As a general observation, we find that exosome depletion mainly leads to the stabilization of RNAs from lowly transcribed loci, including several protein-coding genes. In particular, transcripts that are differentially expressed between states tend to be more exosome sensitive in the state where expression is low. We conclude that the RNA exosome contributes to down-regulation of transcripts with disparate expression, often in conjunction with transcriptional down-regulation.

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The RNA exosome contributes to gene expression regulation during stem cell differentiation [CAGE 2]

Project description:Gene expression programs change during cellular transitions. It is well established that a network of transcription factors and chromatin modifiers regulate RNA levels during embryonic stem cell (ESC) differentiation, but the full impact of post-transcriptional processes remains elusive. While cytoplasmic RNA turnover mechanisms have been implicated in differentiation, the contribution of nuclear RNA decay has not been investigated. Here, we differentiate mouse ESCs, depleted for the ribonucleolytic RNA exosome, into embryoid bodies to determine to which degree RNA abundance in the two states can be attributed to changes in transcription vs. RNA decay by the exosome. As a general observation, we find that exosome depletion mainly leads to the stabilization of RNAs from lowly transcribed loci, including several protein-coding genes. Depletion of the nuclear exosome cofactor RBM7 leads to similar effects. In particular, transcripts that are differentially expressed between states tend to be more exosome sensitive in the state where expression is low. We conclude that the RNA exosome contributes to down-regulation of transcripts with disparate expression, often in conjunction with transcriptional down-regulation.

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The RNA exosome contributes to gene expression regulation during stem cell differentiation [RNA-Seq]

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The RNA exosome contributes to gene expression regulation during stem cell differentiation [PRO-Seq]

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Effect of DUSP6 overexpression or knockdown on gene expression in AML12 cells

Project description:DUSP6 plays important roles in MAPK signaling pathway, but whether and how it is involved in liver funciton remains to be explored. Here, we performed RNA-seq analyses in AML12 cells where DUSP6 is disrupted. We overexpressed GFP-DUSP6 or GFP in AML12 cells, and tested the effects of DUSP6 increase on gene expression in AML12 cells. Meanwhile, we knocked down DUSP6 in AML12 cells and tested the effects of DUSP6 decrease on gene expression in AML12 cells. Taken together, we analyzed the changes of gene expression mediated by DUSP6, which provides new insights for the function of DUSP6 in liver

2023-12-31 | GSE249146 | GEO

The RNA exosome contributes to gene expression regulation during stem cell differentiation [PRO-Seq 2]

Project description:Gene expression programs change during cellular transitions. It is well established that a network of transcription factors and chromatin modifiers regulate RNA levels during embryonic stem cell (ESC) differentiation, but the full impact of post-transcriptional processes remains elusive. While cytoplasmic RNA turnover mechanisms have been implicated in differentiation, the contribution of nuclear RNA decay has not been investigated. Here, we differentiate mouse ESCs, depleted for the ribonucleolytic RNA exosome, into embryoid bodies to determine to which degree RNA abundance in the two states can be attributed to changes in transcription vs. RNA decay by the exosome. As a general observation, we find that exosome depletion mainly leads to the stabilization of RNAs from lowly transcribed loci, including several protein-coding genes. Depletion of the nuclear exosome cofactor RBM7 leads to similar effects. In particular, transcripts that are differentially expressed between states tend to be more exosome sensitive in the state where expression is low. We conclude that the RNA exosome contributes to down-regulation of transcripts with disparate expression, often in conjunction with transcriptional down-regulation.

2018-08-31 | GSE118052 | GEO

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