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

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

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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Crossref · 10.1016/j.cell.2013.12.043

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  • The LIN28/LET-7 pathway has been functionally linked with the Hippo pathway.

    “has been functionally linked with the Hippo pathway (21, 104).”

    From The Hippo signal transduction network for exercise physiologists (2016) · cites this paper as [104]

    The Introduction identifies LIN28A/B as inhibitors of Microprocessor and describes Hippo signaling as a regulator of Microprocessor activity. The Results demonstrate Hippo-dependent processing of other miRNAs, but the passages found do not establish a functional link between the LIN28/LET-7 pathway and Hippo signaling (searched: LIN28, let-7, Hippo and YAP). (LLM, conf=0.73)

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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.
Venue
Cell
Publisher
Elsevier BV
Published
2014-02
Volume
156
Issue
5
Pages
893-906
ISSN
0092-8674 (ISSN-L)
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
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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