Evidence map›Paper›PMID 25033200›Full record

ArticlePloS one2014

Identification of a new target of miR-16, Vacuolar Protein Sorting 4a.

Neeta Adhikari, Weihua Guan, Brian Capaldo, Aaron J Mackey, Marjorie Carlson, Sundaram Ramakrishnan, Dinesha Walek, Manu Gupta, Adam Mitchell, Peter Eckman and 4 more

Open access · goldAbstract readValidation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
0.6field-weighted citation impact, top 33% 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

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Vps4A-mediated tumor suppression upon exosome modulation?Annals of translational medicine · 2016
    Article
  6. 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

14 authors at 6 institutions in 2 countries.

Neeta AdhikariLillehei Heart Institute, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America.
Weihua GuanDivision of Biostatistics, University of Minnesota, Minneapolis, Minnesota, United States of America.
Brian CapaldoCenter for Public Health Genomics, University of Virginia, Charlottesville, Virginia, United States of America.
Aaron J MackeyCenter for Public Health Genomics, University of Virginia, Charlottesville, Virginia, United States of America.
Marjorie CarlsonLillehei Heart Institute, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America.
Sundaram RamakrishnanDepartment of Pharmacology, University of Minnesota, Minneapolis, Minnesota, United States of America.
Dinesha WalekUniversity of Minnesota Genomics Center, University of Minnesota, Minneapolis, Minnesota, United States of America.
Manu GuptaNational Institute of Heart Research, Cardiovascular Biomedical Research Unit, Royal Brompton and Harefield Trust, London, United Kingdom.
Adam MitchellLillehei Heart Institute, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America.
Peter EckmanLillehei Heart Institute, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America.
Ranjit JohnDepartment of Surgery, Cardiothoracic Surgery Division, University of Minnesota, Minneapolis, Minnesota, United States of America.
Euan AshleyCenter for Inherited Cardiovascular Disease, Department of Medicine, Stanford University, Stanford, California, United States of America.
Paul J BartonHeart Science Centre, National Heart and Lung Institute, Imperial College, London, United Kingdom.
Jennifer L HallLillehei Heart Institute, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America.
University of Minnesota · USMinneapolis Heart Institute Foundation · USUniversity of Virginia · USImperial College London · GBNIHR Royal Brompton Cardiovascular Biomedical Research Unit · GBStanford University · US

Funding

Genetic Risk Factors of Myocyte Contractility in Human Heart FailureR21HL104596 · NHLBI · UNIVERSITY OF MINNESOTA · PI HALL, JENNIFER L · 2011 to 2012
$421k
NHLBI NIH HHS 1 R21 HL104596-01NHLBI NIH HHS R21 HL104596
6 · The paper itself

Abstract

rationaleThe rationale was to utilize a bioinformatics approach to identify miRNA binding sites in genes with single nucleotide mutations (SNPs) to discover pathways in heart failure (HF).

objectiveThe objective was to focus on the genes containing miRNA binding sites with miRNAs that were significantly altered in end-stage HF and in response to a left ventricular assist device (LVAD). METHODS AND

resultsBEDTools v2.14.3 was used to discriminate SNPs within predicted 3'UTR miRNA binding sites. A member of the miR-15/107 family, miR-16, was decreased in the circulation of end-stage HF patients and increased in response to a LVAD (p<0.001). MiR-16 decreased Vacuolar Protein Sorting 4a (VPS4a) expression in HEK 293T cells (p<0.01). The SNP rs16958754 was identified in the miR-15/107 family binding site of VPS4a which abolished direct binding of miR-16 to the 3'UTR of VPS4a (p<0.05). VPS4a was increased in the circulation of end-stage HF patients (p<0.001), and led to a decrease in the number of HEK 293T cells in vitro (p<0.001).

conclusionsWe provide evidence that miR-16 decreases in the circulation of end-stage HF patients and increases with a LVAD. Modeling studies suggest that miR-16 binds to and decreases expression of VPS4a. Overexpression of VPS4a decreases cell number. Together, these experiments suggest that miR-16 and VPS4a expression are altered in end-stage HF and in response to unloading with a LVAD. This signaling pathway may lead to reduced circulating cell number in HF.

Indexed as

3' Untranslated RegionsAgedATPases Associated with Diverse Cellular ActivitiesBinding SitesCell LineEndosomal Sorting Complexes Required for TransportFemaleHeart-Assist DevicesHeart FailureHEK293 CellsHumansMaleMicroRNAsMiddle AgedMyocardiumPolymorphism, Single Nucleotide3' Untranslated RegionsATPases Associated with Diverse Cellular ActivitiesEndosomal Sorting Complexes Required for TransportMicroRNAsMIRN16 microRNA, humanVacuolar Proton-Translocating ATPasesVPS4A protein, human

Identifiers

PMID25033200
PMCPMC4102469
OpenAlexW2128211640

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.