RNA-seq profiling of SOX10 knockout A375 melanoma cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE319443 | GEO | 2026/04/29
REPOSITORIES: GEO
Similar Datasets
Project description:SOX10 is a key regulator of melanoma lineage identity, and TADA2B is a component of the SAGA histone acetyltransferase complex. To investigate the transcriptional interplay between SOX10 and TADA2B, bulk RNA sequencing (RNA-seq) was performed in control and TADA2B KO A375 melanoma cells with and without SOX10 overexpression. This dataset enables comparative analysis of gene expression programs associated with SOX10 activation, loss of TADA2B, and their combined perturbation, providing a resource to examine how SAGA-dependent epigenetic regulation influences melanoma transcriptional states.
2026-04-29 | GSE319449 | GEO
Project description:Given the heterogeneous expression of SOX10 in naïve melanoma, we sought to characterize SOX10 deficient population. To this end, we generated SOX10 CRISPR/Cas9 knockouts using two different guide RNAs (gRNA, #2 and #4) in the A375 (BRAF mutant) metastatic cell line. Using this approach, we identified multiple clones with loss of SOX10 expression. RNA-seq was performed to characterize the SOX10-regulated transcriptome. We used GSEA analysis to evaluate significant pathway changes in SOX10 knockout cells when compared to parental cells. We observed an enrichment in pathways associated with the tumor microenvironment (epithelial-mesenchymal transition; TGF beta signaling; extracellular structure organization; apical junction; hypoxia; angiogenesis), alterations in metabolic pathways (increase in the glycolysis pathway), a reduction in MYC and E2F targets and upregulation in p53 pathway and TNFA signaling via NFkB in the SOX10 knockout cells compared to parental cells. SOX10 negative clones have been identified in the minimal residual disease in BRAF mutant PDX models following BRAF and MEK inhibition and in patient samples while on treatment and SOX10 loss has been described as a resistant mechanism in BRAF mutant melanoma patients following vemurafenib treatment. Thus, we also analyzed the transcriptome profile of SOX10 low/deficient cells that arose following BRAFi+MEKi treatment in vivo. We performed GSEA analysis on RNA-seq data of CRT34 and CRT35 cells compared to parental A375 cells. CRT34 and CRT35 showed a very similar transcriptome profile to SOX10 KO cells when compared to A375 parental cells
2022-01-24 | GSE180568 | GEO
Project description:RNA-seq profiling of SOX10 knockout A375 melanoma cells
| PRJNA1423293 | ENA
Project description:RNA-seq profiling of SOX10 overexpression in TADA2B KO A375 melanoma cells
| PRJNA1423302 | ENA
Project description:Microphthalmia-associated transcription factor (MITF) is the master regulator of the melanocyte lineage. By tandem affinity purification and mass spectrometry, we present a comprehensive characterisation of the MITF interactome comprising multiple novel cofactors involved in transcription, DNA replication and repair and chromatin organisation, including a BRG1 chromatin remodelling complex comprising CHD7. BRG1 is essential for melanoma cell proliferation in vitro and for normal melanocyte development in vivo. MITF and SOX10 actively recruit BRG1 to a set of MITF-associated regulatory elements (MAREs) at active enhancers. MITF, SOX10 and YY1 bind between two BRG1-occupied nucleosomes thus defining both a combinatorial signature of transcription factors essential for the melanocyte lineage and a specific chromatin organisation of MAREs. Nevertheless, BRG1 silencing enhances MITF occupancy at MAREs showing that BRG1 acts to promote dynamic MITF interactions with chromatin. 8 samples corresponding to genomic occupancy profiling of MITF, SOX10, BRG1 after si-control, BRG1 after si-MITF and BRG1 after siSOX10; and their respective controls (MITF Input, SOX10 Input, GFP-siCTRL ChIPseq) in 501Mel cells.
2015-04-02 | E-GEOD-61965 | biostudies-arrayexpress
Project description:Using a chromatin regulator-focused shRNA library, we found that suppression of sex determining region Y-box 10 (SOX10) in melanoma causes resistance to BRAF and MEK inhibitors. To investigate how SOX10 loss leads to drug resistance, we performed transcriptome sequencing (RNAseq) of both parental A375 (Ctrl. PLKO) and A375-SOX10KD (shSOX10-1, shSOX10-2) cells. To ask directly whether SOX10 is involved indrug resistance in BRAF(V600E) melanoma patients, we isolated RNA from paired biopsies from melanoma patients (pre- and post- treatment) , that had gained BRAF or MEK inhibitor resistance . We performed RNAseq analysis to determine changes in transcriptome upon drug resistance. Investigate genes regulated by SOX10 and differntial gene expression between pre- and post-treatment biopsies. We use short hairpin RNA to suppression SOX10 in A375 cells and cells were harvested with trizol reagent for RNA isolation. For paired biopsies (patient samples) we collected the first biopsy before the initiation of treatment and the second biopsy after drug resistance developed. RNA was isolated from FFPE samples and subjected for RNA sequencing.
2014-01-04 | E-GEOD-50535 | biostudies-arrayexpress
Project description:We have shown that Sox10 plays a crucial role in the initiation and maintenance of giant congenital nevi and melanoma in a mouse model of melanoma.To dissect the molecular mechanisms and analyze the role of SOX10 in the maintenance of human melanoma, we have performed microarray study. Human melanoma cell line M010817 was transfected with either control shRNA or SOX10 shRNA. RNA was isolated at 48 hours and 96 hours after transfection and subjected to hybridization on Affymetrix microarrays.
2012-07-02 | E-GEOD-37059 | biostudies-arrayexpress
Project description:It is believed that the inherent differentiation program of melanocytes during embryogenesis predisposes melanoma cells to high frequency of metastasis. Sox10, a transcription factor expressed in neural crest stem cells and a subset of progeny lineages, plays a key role in the development of melanocytes. We show that B16F10 melanoma cells transfected with siRNA specific for Sox10 display reduced migratory activity which in turn indicated that a subset of transcriptional regulatory target genes of Sox10 are likely to be involved in migration and metastasis of melanoma cells. We carried out microarray-based gene expression profiling using Sox10-specific siRNA to identify regulatory targets and found that multiple genes including melanocortin-1 receptor (Mc1R) partake in the regulation of migration. We provide evidences that a significant portion of the effect of Sox10 on migration is mediated by Mitf, a transcription factor downstream to Sox10. The involvement of Mc1R in migration was studied in detail in vivo using a murine metastasis model. Specifically, B16F10 melanoma cells treated with a specific siRNA showed reduced tendency in metastasizing to and colonizing the lung after being injected in the tail vein. These data reveal a cadre of novel regulators and mediators involved in migration and metastasis of melanoma cells that represent potential targets of therapeutic intervention. Chemically synthesized siRNA duplex (WT1-Sox10) was used to knock-down the transcription factor Sox10 in murine melanoma cell line B16F10. For the control, siRNA containing 5 nucleotide alterations (MT1-Sox10) were used. Total RNA was subsequently prepared to synthesize probes for microarray screening. A total of three pairs of replicate samples were generated each from separate transfection followed by RNA preparation. Expression values were determined and compared within each pair of WT1-Sox10 and MT1-Sox10 transfections. Genes showing over 2 fold changes in all three replicate pairs were subjected to subsequent analyses.
2010-11-20 | E-GEOD-25501 | biostudies-arrayexpress
Project description:Using a chromatin regulator-focused shRNA library, we found that suppression of sex determining region Y-box 10 (SOX10) in melanoma causes resistance to BRAF and MEK inhibitors. To investigate how SOX10 loss leads to drug resistance, we performed transcriptome sequencing (RNAseq) of both parental A375 (Ctrl. PLKO) and A375-SOX10KD (shSOX10-1, shSOX10-2) cells. To ask directly whether SOX10 is involved indrug resistance in BRAF(V600E) melanoma patients, we isolated RNA from paired biopsies from melanoma patients (pre- and post- treatment) , that had gained BRAF or MEK inhibitor resistance . We performed RNAseq analysis to determine changes in transcriptome upon drug resistance.
2014-01-04 | GSE50535 | GEO
Project description:Microphthalmia-associated transcription factor (MITF) is the master regulator of the melanocyte lineage. By tandem affinity purification and mass spectrometry, we present a comprehensive characterisation of the MITF interactome comprising multiple novel cofactors involved in transcription, DNA replication and repair and chromatin organisation, including a BRG1 chromatin remodelling complex comprising CHD7. BRG1 is essential for melanoma cell proliferation in vitro and for normal melanocyte development in vivo. MITF and SOX10 actively recruit BRG1 to a set of MITF-associated regulatory elements (MAREs) at active enhancers. MITF, SOX10 and YY1 bind between two BRG1-occupied nucleosomes thus defining both a combinatorial signature of transcription factors essential for the melanocyte lineage and a specific chromatin organisation of MAREs. Nevertheless, BRG1 silencing enhances MITF occupancy at MAREs showing that BRG1 acts to promote dynamic MITF interactions with chromatin. 19 samples corresponding to mRNA profiles of 501Mel and Hermes3A after MITF, BRG1 or control shRNA-mediated knockdown were generated by deep sequencing in triplicate (in duplicate for 501_shMITF and corresponding control 501_shSCR2), using HiSeq2500.
2015-04-02 | E-GEOD-61966 | biostudies-arrayexpress