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| Status |
Public on Mar 03, 2014 |
| Title |
Global microRNA expression analysis in HaCaT human keratinocytes transfected with siRNA(s) for p72, NF2/LATS2, DROSHA/DGCR8, or negative control |
| Organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by array
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| Summary |
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.
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| Overall design |
Four conditions (siCtrl, si p72, siNF2/LATS2 and siDROSHA/DGCR8) were analyzed in duplicate.
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| Contributor(s) |
Mori M, Camargo FD, Gregory RI |
| Citation(s) |
24581491 |
| |
| Submission date |
Nov 07, 2013 |
| Last update date |
Mar 10, 2014 |
| Contact name |
Masaki Mori |
| E-mail(s) |
morim@belle.shiga-med.ac.jp
|
| Phone |
+81-775482327
|
| Organization name |
Shiga University of Medical Science
|
| Department |
Molecular Neuroscience Research Center
|
| Street address |
Tsukinowa-cho, Seta
|
| City |
Otsu |
| State/province |
Shiga |
| ZIP/Postal code |
520-2192 |
| Country |
Japan |
| |
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| Platforms (1) |
| GPL17904 |
nCounter Analysis System, nCounter® Human miRNA Expression Assays |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE52276 |
Hippo signaling regulates Microprocessor and links cell density-dependent miRNA biogenesis to cancer |
|
| Relations |
| BioProject |
PRJNA227225 |
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