Cited by 335Hippo pathway signaling and YAP/TAZMicroRNA in disease regulationCancer-related molecular mechanisms research

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Hippo Signaling Regulates Microprocessor and Links Cell-Density-Dependent miRNA Biogenesis to Cancer

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Mori, Masaki, Triboulet, Robinson, Mohseni, Morvarid, Schlegelmilch, Karin, Shrestha, Kriti, Camargo, Fernando D., Gregory, Richard I.·2014·Cell

DOI 10.1016/j.cell.2013.12.043PMC PMC3982296

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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 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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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: Mori, Masaki
Triboulet, Robinson
Mohseni, Morvarid
Schlegelmilch, Karin
Camargo, Fernando D.
Gregory, Richard I.
Venue: Cell
Publisher: Elsevier BV
Published: 2014-02
Volume: 156
Issue: 5
Pages: 893-906
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2013.12.043
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 391 d)
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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Hippo Signaling Regulates Microprocessor and Links Cell-Density-Dependent miRNA Biogenesis to Cancer

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