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Oncogenic Hras-dependent epidermal growth is inhibited following RNAi-mediated depletion of Ctnnb1 and Mllt6

ABSTRACT: Genome-wide RNAi screens in mice identified Ctnnb1 and Mllt6 as physiological regulators of HrasG12V-dependent epidermal hyperplasia. To probe the consequences of Ctnnb1 and Mllt6 on HrasG12V-dependent oncogenic growth, we examined how their depletion impacts gene expression in the HrasoncoX2 epidermis. We performed RNA-seq analysis of FACS-purified embryonic epidermal cells, followed by network analysis of differentially regulated transcripts. Whether Ctnnb1 or Mllt6, knockdown markedly enhanced activity of genes restricting growth, and decreased expression of genes promoting epidermal proliferation. This contrasted with known transcriptional changes that typically follow epidermal expression of oncogenic Hras. Moreover, there was a significant overlap in genes whose expression was affected by Mllt6 and β-catenin, further implying a level of shared function.

ORGANISM(S): Mus musculus

PROVIDER: GSE48480 | GEO | 2013/07/03

SECONDARY ACCESSION(S): PRJNA210306

REPOSITORIES: GEO

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Oncogenic Hras-dependent epidermal growth is inhibited following RNAi-mediated depletion of Ctnnb1 and Mllt6

Project description:Genome-wide RNAi screens in mice identified Ctnnb1 and Mllt6 as physiological regulators of HrasG12V-dependent epidermal hyperplasia. To probe the consequences of Ctnnb1 and Mllt6 on HrasG12V-dependent oncogenic growth, we examined how their depletion impacts gene expression in the HrasoncoX2 epidermis. We performed RNA-seq analysis of FACS-purified embryonic epidermal cells, followed by network analysis of differentially regulated transcripts. Whether Ctnnb1 or Mllt6, knockdown markedly enhanced activity of genes restricting growth, and decreased expression of genes promoting epidermal proliferation. This contrasted with known transcriptional changes that typically follow epidermal expression of oncogenic Hras. Moreover, there was a significant overlap in genes whose expression was affected by Mllt6 and β-catenin, further implying a level of shared function. Transcriptional profiles of epidermal progenitors of embryonic day 18.5 animals of wild-type, HrasG12V, and HrasG12V depleted of Ctnnb1 or Mllt6 backgrounds.

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Normal mouse skin lacking Hras

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Mus musculus

Project description:Oncogenic Hras-dependent epidermal growth is inhibited following RNAi-mediated depletion of Ctnnb1 and Mllt6

| PRJNA210306 | ENA