The bromodomain protein TRIM28 controls the balance between growth and invasiveness in melanoma
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA866358 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR20853484_1.fastq.gz | Fastqsanger.gz | |||
| SRR20853484_2.fastq.gz | Fastqsanger.gz | |||
| SRR20853485_1.fastq.gz | Fastqsanger.gz | |||
| SRR20853485_2.fastq.gz | Fastqsanger.gz | |||
| SRR20853486_1.fastq.gz | Fastqsanger.gz |
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Project description:Melanoma tumors are highly metastatic partly due to the ability of melanoma cells to transition between invasive and proliferative states, however, the mechanisms underlying this plasticity are still not fully understood. To identify new epigenetic regulators of melanoma plasticity, we combined data mining, tumor models, proximity proteomics, and CUT&RUN-sequencing. We focused on the druggable family of bromodomain epigenetic readers, and identified TRIM28 as a new regulator of melanoma plasticity. We found that TRIM28 promotes the expression of pro-invasive genes, and that TRIM28 controls the balance between invasiveness and growth of melanoma cells. We demonstrate that TRIM28 acts via the transcription factor JUNB, that directly regulates the expression of pro-invasive and pro-growth genes. Mechanistically, TRIM28 controls the expression of JUNB by negatively regulating its transcriptional elongation by RNA polymerase II. In conclusion, our results demonstrate that a TRIM28-JUNB axis controls the balance between invasiveness and growth in melanoma tumors and suggests that the bromodomain protein TRIM28 could be targeted to reduce tumor spread.
2022-08-08 | GSE210579 | GEO
Project description:Melanoma tumors are highly metastatic partly due to the ability of melanoma cells to transition between invasive and proliferative states. However, the mechanisms underlying this plasticity are still not fully understood. To identify new epigenetic regulators of melanoma plasticity, we combined data mining, tumor models, proximity proteomics, and CUT&RUN-sequencing. We focus on the druggable family of bromodomain epigenetic readers and identify TRIM28 as a new regulator of melanoma plasticity. We find that TRIM28 promotes the expression of pro-invasive genes, and that TRIM28 controls the balance between invasiveness and growth of melanoma cells. We demonstrate that TRIM28 acts via the transcription factor JUNB, that directly regulates the expression of pro-invasive and pro-growth genes. Mechanistically, TRIM28 controls the expression of JUNB by negatively regulating its transcriptional elongation by RNA polymerase II. In conclusion, our results demonstrate that a TRIM28-JUNB axis controls the balance between invasiveness and growth in melanoma tumors and suggests that the bromodomain protein TRIM28 could be targeted to reduce tumor spread.
| S-SCDT-10_15252-EMBR_202254944 | biostudies-other
Project description:TRIM28 is a bromodomain protein implicated in the regulation of tumor growth. TRIM28 regulates gene expression by recruiting epigenetic writers including HDACs, SETDB1 and HP1. To determine the role of TRIM28 in melanoma cells we knocked down TRIM28 using lentiviral shRNA constructs followed by gene expression analysis using HTA 2.0 GeneChip.
2019-06-21 | GSE133073 | GEO
Project description:Melanoma tumors are highly metastatic partly due to the ability of melanoma cells to transition between invasive and proliferative states. However, the mechanisms underlying this plasticity are still not fully understood. To identify new epigenetic regulators of melanoma plasticity, we combined data mining, tumor models, proximity proteomics, and CUT&RUN sequencing. We focus on the druggable family of bromodomain epigenetic readers and identify TRIM28 as a new regulator of melanoma plasticity. We find that TRIM28 promotes the expression of pro-invasive genes and that TRIM28 controls the balance between invasiveness and growth of melanoma cells. We demonstrate that TRIM28 acts via the transcription factor JUNB that directly regulates the expression of pro-invasive and pro-growth genes. Mechanistically, TRIM28 controls the expression of JUNB by negatively regulating its transcriptional elongation by RNA polymerase II. In conclusion, our results demonstrate that a TRIM28-JUNB axis controls the balance between invasiveness and growth in melanoma tumors and suggest that the bromodomain protein TRIM28 could be targeted to reduce tumor spread.
| S-EPMC9827549 | biostudies-literature
Project description:Transcriptome data after TRIM28 knockdown in A375 melanoma cells
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Project description:Melanoma incidence and mortality rates are historically higher for men than women. Although emerging studies have highlighted tumorigenic roles for the male sex hormone androgen and its receptor (AR) in melanoma, cellular and molecular mechanisms underlying these sex-associated discrepancies are poorly defined. Here, we delineate a previously undisclosed mechanism by which androgen-activated AR transcriptionally upregulates fucosyltransferase 4 (FUT4) expression, which drives melanoma invasiveness by interfering with adherens junctions (AJs). Global phosphoproteomic and fucoproteomic profiling, coupled with in vitro and in vivo functional validation, further reveals that AR-induced FUT4 fucosylates L1 cell adhesion molecule (L1CAM), which is required for FUT4-increased metastatic capacity. Tumor microarray and gene expression analyses demonstrate that AR-FUT4-L1CAM-AJs signaling correlates with pathological staging in melanoma patients. By delineating key androgen-triggered signaling that enhances metastatic aggressiveness, our findings help to explain sex-associated clinical outcome disparities and highlight AR/FUT4 and its effectors as potential prognostic biomarkers and therapeutic targets in melanoma.
2024-01-15 | PXD047337 | Pride
Project description:Melanoma incidence and mortality rates are historically higher for men than women. Although emerging studies have highlighted tumorigenic roles for the male sex hormone androgen and its receptor (AR) in melanoma, cellular and molecular mechanisms underlying these sex-associated discrepancies are poorly defined. Here, we delineate a previously undisclosed mechanism by which androgen-activated AR transcriptionally upregulates fucosyltransferase 4 (FUT4) expression, which drives melanoma invasiveness by interfering with adherens junctions (AJs). Global phosphoproteomic and fucoproteomic profiling, coupled with in vitro and in vivo functional validation, further reveals that AR-induced FUT4 fucosylates L1 cell adhesion molecule (L1CAM), which is required for FUT4-increased metastatic capacity. Tumor microarray and gene expression analyses demonstrate that AR-FUT4-L1CAM-AJs signaling correlates with pathological staging in melanoma patients. By delineating key androgen-triggered signaling that enhances metastatic aggressiveness, our findings help to explain sex-associated clinical outcome disparities and highlight AR/FUT4 and its effectors as potential prognostic biomarkers and therapeutic targets in melanoma.
2024-01-15 | PXD047335 | Pride
Project description:We discovered that Trim28 genetic loss in the adult mouse leads to defective immature erythropoiesis in the bone marrow and consequently to anemia.We further found that TRIM28 controls erythropoiesis in a cell-autonomous manner by inducibly deleting Trim28 exclusively in hematopoietic cells. Finally, in the absence of TRIM28 we observed increased apoptosis as well as diminished expression of multiple erythroid transcription factors and heme biosynthetic enzymes in immature erythroid cells. Thus, TRIM28 is essential for the cell-autonomous development of immature erythroblasts in the bone marrow. To induce Cre recombinase from the Mx1Cre transgene, poly(I:C) was injected 5 times every other day. Mice were analyzed two weeks after completion of poly(I:C) administration. TRIM28 mutant mice generate two distinct types of immature erythroid cells; KOa, with 5-8% of the Trim28 gene remaining undeleted (still bearing 26% of residual mRNA), and KOb, with 1-4% of the gene remaining undeleted (and with 18% of mRNA remaining).
2013-10-04 | E-GEOD-49843 | biostudies-arrayexpress
Project description:Many genes have been implicated in WAT lipid metabolism, including tripartite motif containing 28 (Trim28), a gene proposed to primarily influence adiposity via epigenetic mechanisms in embryonic development. We set out to determine if adipose specific deletion of Trim28 led to changes in adipose tissue function and molecular phenotype. We performed transcriptomics analysis on adipose tissue taken from WT and adipose specific Trim28 KO mice to investigate their molecular phenotype, and to identify pathways altered in KO animals.
2020-11-25 | E-MTAB-9809 | biostudies-arrayexpress
Project description:Ocular melanoma is a common primary malignant ocular tumor in adults with limited effective treatments, so novel therapeutic approaches are desperately needed. Epigenetic regulation plays an important role in tumor development. The SWI/SNF chromatin remodeling complex and bromodomain and extraterminal domain (BET) family proteins are epigenetic regulators involved in several cancers. We aimed to screen a candidate small molecule inhibitor targeting the SWI/SNF complex or BET proteins and investigate its effect and mechanism in ocular melanoma. Colony formation assays were applied to select the most effective candidate inhibitor (JQ-1). We observed phenotypes caused by knockdown of the corresponding gene and synergistic effects with BRD inhibitor (BRDi) treatment and SWI/SNF complex knockdown. We further validated the efficacy of JQ-1 in 10 ocular melanoma cell lines and a mouse xenograft model. The effect of JQ-1 on ocular melanoma cell cycle and apoptosis was analyzed with flow cytometry. We performed RNA sequencing in 2 pairs of ocular melanoma cell lines treated with JQ-1 and control cells treated with DMSO. Gene set enrichment analysis (GSEA) was performed for pathway analysis of the differentially expressed genes (DEGs). We also validated the correlations of DEGs with BRD4 and patient outcomes. Overall, JQ-1 may act downstream of BRD4 and suppress ocular melanoma growth by inducing G1 cell cycle arrest.
2024-07-17 | GSE233589 | GEO