PMID- 24581491
OWN - NLM
STAT- MEDLINE
DCOM- 20140529
LR  - 20240104
IS  - 1097-4172 (Electronic)
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 156
IP  - 5
DP  - 2014 Feb 27
TI  - Hippo signaling regulates microprocessor and links cell-density-dependent miRNA 
      biogenesis to cancer.
PG  - 893-906
LID - S0092-8674(14)00019-1 [pii]
LID - 10.1016/j.cell.2013.12.043 [doi]
AB  - 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.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Mori, Masaki
AU  - Mori M
AD  - Stem Cell Program, Boston Children's Hospital, MA 02115, USA; Department of Stem 
      Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; 
      Department of Biological Chemistry and Molecular Pharmacology and Department of 
      Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell 
      Institute, Boston, MA 02115, USA.
FAU - Triboulet, Robinson
AU  - Triboulet R
AD  - Stem Cell Program, Boston Children's Hospital, MA 02115, USA; Department of 
      Biological Chemistry and Molecular Pharmacology and Department of Pediatrics, 
      Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, 
      Boston, MA 02115, USA.
FAU - Mohseni, Morvarid
AU  - Mohseni M
AD  - Stem Cell Program, Boston Children's Hospital, MA 02115, USA; Department of Stem 
      Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; 
      Harvard Stem Cell Institute, Boston, MA 02115, USA.
FAU - Schlegelmilch, Karin
AU  - Schlegelmilch K
AD  - Stem Cell Program, Boston Children's Hospital, MA 02115, USA; Department of Stem 
      Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; 
      Harvard Stem Cell Institute, Boston, MA 02115, USA.
FAU - Shrestha, Kriti
AU  - Shrestha K
AD  - Stem Cell Program, Boston Children's Hospital, MA 02115, USA; Department of Stem 
      Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; 
      Harvard Stem Cell Institute, Boston, MA 02115, USA.
FAU - Camargo, Fernando D
AU  - Camargo FD
AD  - Stem Cell Program, Boston Children's Hospital, MA 02115, USA; Department of Stem 
      Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; 
      Harvard Stem Cell Institute, Boston, MA 02115, USA. Electronic address: 
      fernando.camargo@childrens.harvard.edu.
FAU - Gregory, Richard I
AU  - Gregory RI
AD  - Stem Cell Program, Boston Children's Hospital, MA 02115, USA; Department of 
      Biological Chemistry and Molecular Pharmacology and Department of Pediatrics, 
      Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, 
      Boston, MA 02115, USA. Electronic address: rgregory@enders.tch.harvard.edu.
LA  - eng
SI  - GEO/GSE49384
SI  - GEO/GSE52276
GR  - R01GM086386/GM/NIGMS NIH HHS/United States
GR  - R01 GM086386/GM/NIGMS NIH HHS/United States
GR  - R01 AR064036/AR/NIAMS NIH HHS/United States
GR  - R01 CA131426/CA/NCI NIH HHS/United States
GR  - P30 DK034854/DK/NIDDK NIH HHS/United States
GR  - R01 CA131426,/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (MYC protein, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - 0 (Transcription Factors)
RN  - 0 (YY1AP1 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 3.6.1.- (DDX17 protein, human)
RN  - EC 3.6.4.13 (DEAD-box RNA Helicases)
SB  - IM
CIN - Nat Rev Cancer. 2014 Apr;14(4):216-7. PMID: 24658271
MH  - Cell Count
MH  - Cell Cycle Proteins
MH  - Cell Line
MH  - DEAD-box RNA Helicases/metabolism
MH  - Hippo Signaling Pathway
MH  - Humans
MH  - MicroRNAs/genetics/*metabolism
MH  - Neoplasms/*genetics
MH  - Nuclear Proteins/metabolism
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Proto-Oncogene Proteins c-myc/metabolism
MH  - Signal Transduction
MH  - Transcription Factors/metabolism
MH  - Transcriptome
PMC - PMC3982296
MID - NIHMS568884
EDAT- 2014/03/04 06:00
MHDA- 2014/05/30 06:00
PMCR- 2015/02/27
CRDT- 2014/03/04 06:00
PHST- 2013/08/07 00:00 [received]
PHST- 2013/11/21 00:00 [revised]
PHST- 2013/12/31 00:00 [accepted]
PHST- 2014/03/04 06:00 [entrez]
PHST- 2014/03/04 06:00 [pubmed]
PHST- 2014/05/30 06:00 [medline]
PHST- 2015/02/27 00:00 [pmc-release]
AID - S0092-8674(14)00019-1 [pii]
AID - 10.1016/j.cell.2013.12.043 [doi]
PST - ppublish
SO  - Cell. 2014 Feb 27;156(5):893-906. doi: 10.1016/j.cell.2013.12.043.