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Transcriptomic analysis of D458 medulloblastoma cells treated with 10nM THZ1 or DMSO in comparison to shNull and shCDK7-1,-2,-3 genetic knockdown cell lines

ABSTRACT: Transcriptomic analysis of D458 medulloblastoma cells treated with 10nM THZ1 or DMSO in comparison to shNull and shCDK7-1,-2,-3 genetic knockdown cell lines

PROVIDER: PRJNA692469 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13444341_1.fastq.gz	Fastqsanger.gz
	SRR13444341_2.fastq.gz	Fastqsanger.gz
	SRR13444342_1.fastq.gz	Fastqsanger.gz
	SRR13444342_2.fastq.gz	Fastqsanger.gz
	SRR13444343_1.fastq.gz	Fastqsanger.gz

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Transcriptomic analysis of D458 medulloblastoma cells treated with 10nM THZ1 or DMSO in comparison to shNull and shCDK7-1,-2,-3 genetic knockdown cell lines

Project description:The goal of this study was to first determine the effect of CDK7 chemical inhibition (THZ1) on global gene expression. Then to observe and compare to the transcriptomic profile of CDK7 genetic knockdown in D458 medulloblastoma cells.

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Project description:Purpose: To assess THZ1-induced global changes of transcriptome of Hh-driven cancer Methods: SMB56 or SMB56-shSufu cells were mouse hedgehog-driven medulloblastoma cell lines that are either responsive or resistant to SMO inhibitor (GDC-0449). They were treated with 0.1 uM THZ1 or DMSO for 8 hours. 1 uM GDC-0449 treated SMB56 cells were included as control. Gene expression profiles were generated by RNAseq, in duplicate, using Hiseq3000. The RNAseq reads were mapped to the hg19 reference genome using STAR (v2.5.3a). Expression levels for each sample were quantified to FPKM using Cufflinks (v2.2.1). Differential expression analysis was carried out using R package DESeq2 (v1.20.0) Results: Compared to GDC-0449 treatment in SMB56 cells, THZ1 induced a robust global transcriptional downregulation in both SMB56 and SMB56-shSufu cells. When we compared the top 2000 significantly downregulated genes between THZ1-treated SMB56 and SMB56-shSufu cells, we found they had ~70% in common. GSEA reveals Hh-target genes are enriched in DMSO treated cells versus THZ1-treated ones. Conclusions: CDK7 inhibition induced a robust and similar transcriptional downregulation in both SMB56 and SMB56-shSufu cells, with preferential targeting of Hh pathway transcriptional output.

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