Evidence map›Paper›PMID 28984049›Full record

ArticleJournal of cachexia, sarcopenia and muscle2018

miR-422a suppresses SMAD4 protein expression and promotes resistance to muscle loss.

Richard Paul, Jen Lee, Anna V Donaldson, Martin Connolly, Mohammad Sharif, Samantha Amanda Natanek, Ulrich Rosendahl, Michael I Polkey, Mark Griffiths, Paul R Kemp

Open access · goldAbstract read
In one paragraph

Article in Journal of cachexia, sarcopenia and muscle, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

22 citing papers in PubMed, 36 citations in OpenAlex.

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  9. Hsa-Mir-320c, Hsa-Mir-200c-3p, and Hsa-Mir-449c-5p as Potential Specific miRNA Biomarkers of COPD: A Pilot Study.Pathophysiology : the official journal of the International Society for Pathophysiology · 2022
    Article
  10. Biomarkers for cancer cachexia: where do we stand?Journal of cachexia, sarcopenia and muscle · 2020
    Article
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  12. Review
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  19. MicroRNAs in muscle wasting.Journal of cachexia, sarcopenia and muscle · 2018
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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

10 authors at 4 institutions in 2 countries.

Richard PaulMolecular Medicine Section, National Heart & Lung Institute, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK.
Jen LeeMolecular Medicine Section, National Heart & Lung Institute, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK.
Anna V DonaldsonMolecular Medicine Section, National Heart & Lung Institute, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK.
Martin ConnollyMolecular Medicine Section, National Heart & Lung Institute, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK.
Mohammad SharifMolecular Medicine Section, National Heart & Lung Institute, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK.
Samantha Amanda NatanekMolecular Medicine Section, National Heart & Lung Institute, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK.
Ulrich RosendahlDepartment of Cardiothoracic Surgery, Royal Brompton and Harefield NHS Foundation Trust, London, SW3 6NP, UK.
Michael I PolkeyNational Institute for Health Research Respiratory Biomedical Research Unit at Royal Brompton and Harefield NHS Foundation Trust and Imperial College, London, SW3 6NP, UK.
Mark GriffithsInflammation, Regeneration and Development, National Heart and Lung Institute, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK.
Paul R KempMolecular Medicine Section, National Heart & Lung Institute, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK.
Imperial College London · GBLung Institute · USNational Institute for Health Research · GBRoyal Brompton & Harefield NHS Foundation Trust · GB

Funding

British Heart Foundation FS/14/71/31038
6 · The paper itself

Abstract

backgroundLoss of muscle mass and strength are important sequelae of chronic disease, but the response of individuals is remarkably variable, suggesting important genetic and epigenetic modulators of muscle homeostasis. Such factors are likely to modify the activity of pathways that regulate wasting, but to date, few such factors have been identified.

methodsThe effect of miR-422a on SMAD4 expression and transforming growth factor (TGF)-β signalling were determined by western blotting and luciferase assay. miRNA expression was determined by qPCR in plasma and muscle biopsy samples from a cross-sectional study of patients with chronic obstructive pulmonary disease (COPD) and a longitudinal study of patients undergoing aortic surgery, who were subsequently admitted to the intensive care unit (ICU).

resultsmiR-422a was identified, by a screen, as a microRNA that was present in the plasma of patients with COPD and negatively associated with muscle strength as well as being readily detectable in the muscle of patients. In vitro, miR-422a suppressed SMAD4 expression and inhibited TGF-beta and bone morphogenetic protein-dependent luciferase activity in muscle cells. In male patients with COPD and those undergoing aortic surgery and on the ICU, a model of ICU-associated muscle weakness, quadriceps expression of miR-422a was positively associated with muscle strength (maximal voluntary contraction r = 0.59, P < 0.001 and r = 0.51, P = 0.004, for COPD and aortic surgery, respectively). Furthermore, pre-surgery levels of miR-422a were inversely associated with the amount of muscle that would be lost in the first post-operative week (r = -0.57, P < 0.001).

conclusionsThese data suggest that differences in miR-422a expression contribute to the susceptibility to muscle wasting associated with chronic and acute disease and that at least part of this activity may be mediated by reduced TGF-beta signalling in skeletal muscle.

Indexed as

AgedCell LineCohort StudiesCross-Sectional StudiesFemaleHumansMaleMicroRNAsMiddle AgedMuscle, SkeletalMuscle WeaknessPulmonary Disease, Chronic ObstructiveSignal TransductionSmad4 ProteinTransfectionTransforming Growth Factor betaMicroRNAsMIRN422 microRNA, humanSmad4 ProteinSMAD4 protein, humanTransforming Growth Factor betaMicroRNAMuscle wastingSusceptibilityTGF-beta signalling

Identifiers

PMID28984049
PMCPMC5803610
OpenAlexW2762996613

What OpenQuestion holds

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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.