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Single-cell RNA-Seq Profiling of the Transcriptomic Response to RB Loss in the Retinoblastoma Cell of Origin

ABSTRACT: Single-cell RNA-Seq Profiling of the Transcriptomic Response to RB Loss in the Retinoblastoma Cell of Origin

PROVIDER: PRJNA927001 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23209100_1.fastq.gz	Fastqsanger.gz
	SRR23209100_2.fastq.gz	Fastqsanger.gz
	SRR23209200_1.fastq.gz	Fastqsanger.gz
	SRR23209200_2.fastq.gz	Fastqsanger.gz
	SRR23209300_1.fastq.gz	Fastqsanger.gz

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Single-cell RNA-Seq Profiling of the Transcriptomic Response to RB Loss in the Retinoblastoma Cell of Origin

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Project description:Although Dicer1 functions as a haploinsufficient tumour suppressor its complete loss of function is selected against during tumourigenesis. Here we show that homozygous loss of Dicer1 prevents retinoblastoma formation in mice by synthetic lethality with combined inactivation of the p53 and Rb tumor suppressor pathways. We show that Dicer1 deficiency is tolerated in Rb-deficient retinal progenitor cells harbouring an intact p53 pathway, but not in absence of p53. The synthetic lethal interaction is mediated by the oncogenic miR-17∼92 cluster since its deletion phenocopies Dicer1 loss in this context. Accordingly, miR-17∼92- inactivation suppresses retinoblastoma formation in mice and co-silencing of miR17/20a and p53 cooperatively decrease the viability of pre-formed human retinoblastoma cells. These data provide important insights into what underlies selective pressure against loss of Dicer1 during tumorigenesis and indicate that targeting Dicer or miR-17-20a family members should be explored as a potential selective therapeutic approach for retinoblastoma prevention and/or treatment.

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