Transcriptomics,Genomics

Dataset Information

24

Transcription Factor Activating Protein 4 is synthetically lethal and a master regulator of MYCN-amplified neuroblastoma


ABSTRACT: Despite the identification of MYCN amplification as an adverse prognostic marker in neuroblastoma, MYCN inhibitors have yet to be developed. Here, by integrating evidence from a whole genome shRNA library screen and the computational inference of master regulator proteins, we identify Transcription Factor Activating Protein 4 (TFAP4) as a critical effector of MYCN amplification in neuroblastoma, providing a novel synthetic lethal target. We demonstrate that TFAP4 is a direct target of MYCN in neuroblastoma cells, and that its expression and activity strongly negatively correlate with neuroblastoma patient survival. Silencing TFAP4 selectively inhibits MYCN-amplified neuroblastoma cell growth both in vitro and in vivo, in xenograft mouse models. Mechanistically, silencing TFAP4 induces neuroblastoma differentiation, as evidenced by increased neurite outgrowth and up-regulation of neuronal markers. Taken together, our results demonstrate that TFAP4 is a master regulator of MYCN-amplified neuroblastoma and may represent a valuable novel therapeutic target. Overall design: Control and TFAP4 KD RNA-seq in two neuroblastoma cell lines **Please note that raw data for the following 7 samples have been lost and thus are not included in the current records; GSM2742417 - SKNDZ Control RNASeq [SD013] GSM2742419 - SKNDZ TFAP4 KD RNASeq [SD008] GSM2742420 - SKNDZ TFAP4 KD RNASeq [SD0014] GSM2742422 - NGP Control RNASeq [SD011] GSM2742423 - NGP Control RNASeq [SD017] GSM2742425 - NGP TFAP4 KD RNASeq [SD012] GSM2742426 - NGP TFAP4 KD RNASeq [SD018]

INSTRUMENT(S): Illumina HiSeq 2000 (Homo sapiens)

SUBMITTER: Gonzalo Lopez 

PROVIDER: GSE102652 | GEO | 2017-11-15

SECONDARY ACCESSION(S): PRJNA398270

REPOSITORIES: GEO

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