Evidence map›Paper›PMID 26658687›Full record

ArticleJournal of hepatology2016

RNAi-nanoparticulate manipulation of gene expression as a new functional genomics tool in the liver.

Hao Yin, Roman L Bogorad, Carmen Barnes, Stephen Walsh, Iris Zhuang, Hidenori Nonaka, Vera Ruda, Satya Kuchimanchi, Lubomir Nechev, Akin Akinc and 5 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of hepatology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.5field-weighted citation impact, top 35% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Article
  3. Hippo signalling in the liver: role in development, regeneration and disease.Nature reviews. Gastroenterology & hepatology · 2022
    Review
  4. Review
  5. Article
  6. Hippo Signaling in the Liver - A Long and Ever-Expanding Story.Frontiers in cell and developmental biology · 2019
    Article
  7. Delivery technologies for genome editing.Nature reviews. Drug discovery · 2017
    Review
  8. Article
  9. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 6 institutions in 3 countries.

Hao YinDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Roman L BogoradDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Carmen BarnesAlnylam Pharmaceuticals, Cambridge, MA 02142, USA.
Stephen WalshDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Iris ZhuangDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Hidenori NonakaMax Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Dresden 01307, Germany.
Vera RudaDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Satya KuchimanchiAlnylam Pharmaceuticals, Cambridge, MA 02142, USA.
Lubomir NechevAlnylam Pharmaceuticals, Cambridge, MA 02142, USA.
Akin AkincAlnylam Pharmaceuticals, Cambridge, MA 02142, USA.
Wen XueRNA Therapeutics Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Marino ZerialMax Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Dresden 01307, Germany.
Robert LangerDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Harvard-MIT Division of Health Sciences & Technology, Cambridge, MA 02139, USA; Institute of Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Daniel G AndersonDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Harvard-MIT Division of Health Sciences & Technology, Cambridge, MA 02139, USA; Institute of Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: dgander@mit.edu.
Victor KotelianskySkolkovo Institute of Science and Technology, Skolkovo 143025, Russia; Department of Chemistry, M.V. Lomonosov Moscow State University, Leninskie Gory 119991, Russia. Electronic address: V.Kotelianski@Skoltech.RU.
Massachusetts Institute of Technology · USAlnylam Pharmaceuticals (United States) · USMax Planck Institute of Molecular Cell Biology and Genetics · DEHarvard–MIT Division of Health Sciences and Technology · USLomonosov Moscow State University · RUUniversity of Massachusetts Chan Medical School · US

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI MATTHEW G. VANDER HEIDEN · 1985 to 2026
$93.9M
The Development of Clinical Grade, Targeted Magnetic NanoparticlesU54CA151884 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI LANGER, ROBERT SAMUEL · 2010 to 2014
$11.3M
High-Throughput Craniofacial tissue engineeringR01DE016516 · NIDCR · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI LANGER, ROBERT SAMUEL · 2005 to 2014
$3.8M
Investigating microRNA miR-34a in lung cancer development and therapyR00CA169512 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI XUE, WEN · 2014 to 2016
$747k
NCI NIH HHS 5R00CA169512NCI NIH HHS 5-U54-CA151884-04NCI NIH HHS P30 CA014051NCI NIH HHS P30-CA14051NCI NIH HHS R00 CA169512NCI NIH HHS U54 CA151884NIDCR NIH HHS R01 DE016516NIDCR NIH HHS R01-DE016516
6 · The paper itself

Abstract

BACKGROUND &

aimsThe Hippo pathway controls organ size through a negative regulation of the transcription co-activator Yap1. The overexpression of hyperactive mutant Yap1 or deletion of key components in the Hippo pathway leads to increased organ size in different species. Analysis of interactions of this pathway with other cellular signals corroborating organ size control is limited in part due to the difficulties associated with development of rodent models.

methodsHere, we develop a new model of reversible induction of the liver size in mice using siRNA-nanoparticles targeting two kinases of the Hippo pathway, namely, mammalian Ste20 family kinases 1 and 2 (Mst1 and Mst2), and an upstream regulator, neurofibromatosis type II (Nf2).

resultsThe triple siRNAs nanoparticle-induced hepatomegaly in mice phenocopies one observed with Mst1(-/-)Mst2(-/-) liver-specific depletion, as shown by extensive proliferation of hepatocytes and activation of Yap1. The simultaneous co-treatment with a fourth siRNA nanoparticle against Yap1 fully blocked the liver growth. Hippo pathway-induced liver enlargement is associated with p53 activation, evidenced by its accumulation in the nuclei and upregulation of its target genes. Moreover, injections of the triple siRNAs nanoparticle in p53(LSL/LSL) mice shows that livers lacking p53 expression grow faster and exceed the size of livers in p53 wild-type animals, indicating a role of p53 in controlling Yap1-induced liver growth.

conclusionOur data show that siRNA-nanoparticulate manipulation of gene expression can provide the reversible control of organ size in adult animals, which presents a new avenue for the investigation of complex regulatory networks in liver.

Indexed as

NanoparticlesRNA InterferenceAdaptor Proteins, Signal TransducingAnimalsCell Cycle ProteinsGene ExpressionGenes, Neurofibromatosis 2GenomicsHepatocyte Growth FactorHepatomegalyHippo KinasesLiverMiceMice, Inbred C57BLOrgan SizePhosphoproteinsAdaptor Proteins, Signal TransducingCell Cycle ProteinsHepatocyte Growth FactorHippo Kinasesmacrophage stimulating proteinPhosphoproteinsProtein Serine-Threonine KinasesProto-Oncogene ProteinsSerine-Threonine Kinase 3Stk3 protein, mouseTumor Suppressor Protein p53Yap1 protein, mouseYAP-Signaling ProteinsBile acidsHippo pathwayNanoparticlesp53siRNA

Identifiers

PMID26658687
PMCPMC5381270
OpenAlexW2288182265

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.