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Global microRNA expression analysis in HaCaT human keratinocytes transfected with p72 or control EGFP in addition to siRNAs for NF2 and LATS2.

ABSTRACT: Global downregulation of microRNAs (miRNAs) is commonly observed in human cancers and can have a causative role in tumorigenesis. The mechanisms responsible for this phenomenon remain poorly understood. Here we show that YAP, the downstream target of the tumor-suppressive Hippo signaling pathway regulates miRNA biogenesis in a cell density-dependent manner. At low cell density, nuclear YAP binds and sequesters p72 (DDX17), a regulatory component of the miRNA processing machinery. At high cell density, Hippo-mediated cytoplasmic retention of YAP facilitates p72 association with Microprocessor and binding to a specific sequence motif in pri-miRNAs. Inactivation of the Hippo pathway or expression of constitutively active YAP causes widespread miRNA suppression in cells and tumors and a corresponding post-transcriptional induction of MYC expression. Thus, the Hippo pathway links contact-inhibition regulation to miRNA biogenesis and may be responsible for the widespread miRNA repression observed in cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE52205 | GEO | 2014/03/03

SECONDARY ACCESSION(S): PRJNA227229

REPOSITORIES: GEO

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Global microRNA expression analysis in HaCaT human keratinocytes transfected with siRNA(s) for p72, NF2/LATS2, DROSHA/DGCR8, or negative control

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