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RNA-seq analysis after LMO1 or MYCN knockdown in Kelly cells

ABSTRACT: RNA-seq analysis was performed in Kelly neuroblastoma cell line to analyze gene expression changes after LMO1 or MYCN knockdown.

ORGANISM(S): Homo sapiens

PROVIDER: GSE118823 | GEO | 2019/11/10

REPOSITORIES: GEO

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RNA-seq analysis after LMO1 or MYCN knockdown in Kelly cells

Project description:RNA-seq analysis after LMO1 or MYCN knockdown in Kelly cells

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Project description:Neuroblastoma is an embryonal tumor of the peripheral sympathetic nervous system. Elevated expression of the transcription factor LMO1 and the polymorphisms within this gene are associated with the susceptibility to develop neuroblastoma. LMO1 has been implicated as an oncogene in T-cell acute lymphoblastic leukemia; however, the transcriptional targets regulated by this protein in neuroblastoma cells are unknown. Here, we identify the genes and molecular pathways controlled by LMO1 in neuroblastoma cells. ChIP-seq analysis revealed that LMO1-bound regions are frequently co-occupied by GATA3 and MYCN proteins and are associated with active histone marks in neuroblastoma cells. RNA-seq analysis demonstrated that LMO1 regulates gene expression in a tumor type-specific manner. One high-confidence target gene directly regulated by LMO1 and MYCN is ASCL1, which is more highly expressed in adrenergic subtype of neuroblastoma cells as compared to normal neuronal cells. High levels of ASCL1 expression are associated with inferior overall survival in primary human neuroblastoma cases. ChIP-seq analysis identified a regulatory element controlling ASCL1 expression that is bound by LMO1, MYCN and the members of the core regulatory circuitry in neuroblastoma cells. Furthermore, ASCL1 is required for neuroblastoma cell growth and regulates genes responsible for repression of neuronal cell differentiation. Taken together, our results implicate ASCL1 as a critical downstream target of LMO1 in the molecular pathogenesis of neuroblastoma.

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Gene expression profile of human neuroblastoma cell line SHSY-5Y after LMO1 knockdown

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Project description:The MYCN locus is amplified in about half of high-risk neuroblastoma tumors. To identify genomic loci occupied by MYCN protein in the MYCN-amplified neuroblastoma cell lines NGP, Kelly and NB-1643, we performed chromatin immunoprecipitation coupled with Next-Generation Sequencing (ChIP-seq) using an anti-MYCN antibody.

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Targeting EZH2 in MYCN-amplified Neuroblastoma [ChIP-seq]

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RNA-seq of IMR-5/75 neuroblastoma cell line upon TBX2 and/or MYCN knockdown

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