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YTHDF2 iCLIP in glioblastoma stem cells

ABSTRACT: YTHDF2 iCLIP in glioblastoma stem cells

PROVIDER: PRJNA663772 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12650379_1.fastq.gz	Fastqsanger.gz
	SRR12650379_2.fastq.gz	Fastqsanger.gz
	SRR12650380_1.fastq.gz	Fastqsanger.gz
	SRR12650380_2.fastq.gz	Fastqsanger.gz
	SRR12650381_1.fastq.gz	Fastqsanger.gz

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YTHDF2 iCLIP in glioblastoma stem cells

Project description:Glioblastoma is a universally lethal cancer driven by glioblastoma stem cells (GSCs). Here, we interrogated N6-methyladenosine (m6A) mRNA modifications in GSCs by methyl RNA-immunoprecipitation followed by sequencing (meRIP-seq) and transcriptome analysis, finding transcripts marked by m6A often upregulated. Interrogating m6A regulators, GSCs displayed preferential expression as well as in vitro and in vivo dependency of the m6A reader, YTHDF2, in contrast to normal neural stem cells (NSCs). While YTHDF2 has been reported to destabilize mRNAs, YTHDF2 stabilized the oncogene transcripts, MYC and VEGFA, in GSCs in an m6A-dependent manner. We identified IGFBP3 as a downstream effector of the YTHDF2-MYC axis in GSCs and IGF1/IGF1R inhibitor, Linsitinib, as preferentially targeting YTHDF2-expressing cells, inhibiting the viability of GSCs without affecting NSCs and impairing in vivo glioblastoma growth. Thus, YTHDF2 links RNA epitranscriptomic modifications and GSC growth, laying the foundation for the YTHDF2-MYC-IGFBP3 axis as a specific and novel therapeutic target in glioblastoma.

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The RNA m6A reader YTHDF2 maintains oncogene expression and is a targetable dependency in glioblastoma stem cells [RNA-seq]

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The RNA m6A reader YTHDF2 maintains oncogene expression and is a targetable dependency in glioblastoma stem cells [m6A RIP-seq]

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Microarray analysis of YTHDF2-deficient leukemic stem cells

Project description:YTHDF2 is overexpressed in a broad spectrum of human acute myeloid leukemias (AML). To study the role of YTHDF2 in leukemia, total RNA from Ythdf2CKO (n=4) and Ythdf2CTL (n=4) leukemic stem cells were used for Affymetrix global gene expression analysis.

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