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The role of CDK7 in cutaneous melanoma

ABSTRACT: The role of CDK7 in cutaneous melanoma

PROVIDER: PRJNA664045 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12659700_1.fastq.gz	Fastqsanger.gz
	SRR12659700_2.fastq.gz	Fastqsanger.gz
	SRR12659701_1.fastq.gz	Fastqsanger.gz
	SRR12659701_2.fastq.gz	Fastqsanger.gz
	SRR12659702.fastq.gz	Fastqsanger.gz

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Genome-wide distribution of CDK7 in human cutaneous melanoma

Project description:CDK7 is a cycline-dependent kinase part of the basal transcription factor TFIIH involved in the formation of the pre-inithiation complex of RNApol II dependent-genes. Despite it's well known genomic localization at the level of gene's promoter, it has been recently observed from Kwiatkowski et al., (2014) that CDK7 can be found also in large clusters of gene regulatory elements called Super-enhancers (SEs) of both normal and cancer cells. Here we report that CDK7 is resembling such distribution in a human melanoma context, in particular at the level of genes important in melanoma physiology such as the master transcription factors MITF and SOX10 which indeed, following the inhibition of CDK7 with the molecule THZ1, are rapidly downregulated at very low nanomolar concentration.

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Genome-wide distribution of CDK7 in human cutaneous melanoma

Project description:Genome-wide distribution of CDK7 in human cutaneous melanoma

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CDK7 Inhibition Suppresses Melanoma Growth By Depleting A Super-enhancer Associated "Achilles" Lineage Cluster [ChIP-Seq]

Project description:Cutaneous malignant melanoma (CMM) lacks targeted therapies beyond the oft-circumvented BRAF inhibitors. Part of the difficulty in treating melanomas has been attributed to a strong survival program controlled by melanocyte transcription factors such as MITF - a phenomenon first described in melanoma as “lineage dependency.” Recently, a highly selective covalent CDK7 inhibitor (THZ1) has been shown to potently suppress the growth of various cancers through the depletion of master transcription-regulating oncogenes and the disruption of their attendant super-enhancers. We now show that melanoma cells are highly sensitive to CDK7 inhibition and that a melanocyte “lineage cluster,” whose members are transcriptionally driven by super-enhancers, is also strongly suppressed by THZ1. These results point to CDK7 inhibition as a viable strategy to deprive oncogenic transcription and suppress tumor growth in melanoma.

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microRNA expression in ulcerated primary cutaneous melanoma

Project description:microRNA expression in RNA isolated from formalin fixed, paraffin embedded tissue from ulcerated primary cutaneous melanoma compared to non-ulcerated primary cutaneous melanoma

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Project description:mRNA expression in RNA isolated from formalin fixed, paraffin embedded tissue from ulcerated primary cutaneous melanoma compared to non-ulcerated primary cutaneous melanoma

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Comparative microarray analysis of microRNA expression profiles in primary cutaneous malignant melanoma, cutaneous malignant melanoma metastases and benign melanocytic naevi

Project description:Perturbations in microRNA (miRNA) expression profiles has been reported for cutaneous malignant melanoma (CMM). With regards to a rapidly growing number of newly discovered miRNA sequences, the availability of up-to-date miRNA expression profiles for primary cutaneous malignant melanoma (PCMM), cutaneous malignant melanoma metastases (CMMM) and benign melanocytic naevi (BMN) is limited. Patients with PCMM (n=9), CMMM (n=4) and BMN (n=8) were included in the study. Specimens were obtained during surgery from the center of the tumors (lesional). An exploratory microarray analysis was performed by miRNA expression profiling based on miRBase V.16. Additionally, the expression levels of selected miRNA candidates were confirmed by TaqMan real-time quantitative polymerase chain reaction (RT-PCR). New miRNA candidates previously not described to be associated with CMM were found to be potentially dysregulated in CMM.

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