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Hippo Signaling Regulates Microprocessor and Links Cell-Density-Dependent miRNA Biogenesis to Cancer
Open accessAbstract
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 posttranscriptional 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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“has been functionally linked with the Hippo pathway (21, 104).”
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Metadata
- Authors
- Mori, M., Triboulet, R., Mohseni, M., Schlegelmilch, K., Shrestha, K., Camargo, F. D., & Gregory, R. I.
- Affiliations
- Boston Children's Hospital (US)
- Corresponding author
- Camargo, Fernando D.
- Gregory, Richard I.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-02
- Volume
- 156
- Issue
- 5
- Pages
- 893-906
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3982296
- OpenAlex
- W2166840595
- Cited by
- 335
- References
- 65
- Citations by year
- 2026: 9 · 2025: 5 · 2024: 16 · 2023: 11 · 2022: 30 · 2021: 35 · 2020: 30 · 2019: 34 · 2018: 35 · 2017: 24 · 2016: 37 · 2015: 41 · 2014: 28
- FWCI
- 21.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Japan Heart Foundation
- Stand Up To Cancer
- Bayer Yakuhin
- National Cancer Institute (R01CA131426)
- National Institute of General Medical Sciences (R01GM086386)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK034854)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR064036)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- Hippo signaling pathway, YAP, microRNA biogenesis, microprocessors, DDX17, cell density, contact inhibition, pri-miRNA processing, MYC expression
- MeSH terms
- Hippo Signaling Pathway, Cell Count, Cell Line, Humans, Neoplasms, Nuclear Proteins, Transcription Factors, Signal Transduction, Proto-Oncogene Proteins c-myc, Protein Serine-Threonine Kinases, Cell Cycle Proteins, MicroRNAs, DEAD-box RNA Helicases, Transcriptome
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