Evidence map›Paper›PMID 26133785›Full record

ArticleGene therapy2015

miR-16 rescues F508del-CFTR function in native cystic fibrosis epithelial cells.

P Kumar, S Bhattacharyya, K W Peters, M L Glover, A Sen, R T Cox, S Kundu, H Caohuy, R A Frizzell, H B Pollard and 1 more

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

Article in Gene therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 11% 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

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
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  10. Review
  11. Barriers to inhaled gene therapy of obstructive lung diseases: A review.Journal of controlled release : official journal of the Controlled Release Society · 2016
    Review
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

11 authors at 2 institutions in 1 country.

P KumarDepartment of Anatomy, Physiology and Genetics, Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
S BhattacharyyaDepartment of Anatomy, Physiology and Genetics, Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
K W PetersDepartment of Cell Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
M L GloverDepartment of Cell Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
A SenDepartment of Biochemistry and Molecular Biology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
R T CoxDepartment of Biochemistry and Molecular Biology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
S KunduDepartment of Anatomy, Physiology and Genetics, Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
H CaohuyDepartment of Anatomy, Physiology and Genetics, Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
R A FrizzellDepartment of Cell Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
H B PollardDepartment of Anatomy, Physiology and Genetics, Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
R BiswasDepartment of Anatomy, Physiology and Genetics, Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Uniformed Services University of the Health Sciences · USUniversity of Pittsburgh · US

Funding

Translational StudiesP30DK072506 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI PILEWSKI, JOSEPH MARK · 2005 to 2017
$12.5M
Co-chaperone Actions in CFTR BiogenesisR01DK068196 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GOETZMAN, ERIC S · 2004 to 2024
$5.8M
NIDDK NIH HHS DK068196NIDDK NIH HHS DK072506NIDDK NIH HHS P30 DK072506NIDDK NIH HHS R01 DK068196
6 · The paper itself

Abstract

Cystic fibrosis (CF) is due to mutations in the CFTR gene, which prevents correct folding, trafficking and function of the mutant cystic fibrosis transmembrane conductance regulator (CFTR) protein. The dysfunctional effect of CFTR mutations, principally the F508del-CFTR mutant, is further manifested by hypersecretion of the pro-inflammatory chemokine interleukin-8 into the airway lumen, which further contributes to morbidity and mortality. We have hypothesized that microRNA (miR)-based therapeutics could rescue the dysfunctional consequences of mutant CFTR. Here we report that a miR-16 mimic can effectively rescue F508del-CFTR protein function in airway cell lines and primary cultures, of differentiated human bronchial epithelia from F508del homozygotes, which express mutant CFTR endogenously. We also identify two other miRs, miR-1 and miR-302a, which are also active. Although miR-16 is expressed at basal comparable levels in CF and control cells, miR-1 and miR-302a are undetectable. When miR mimics are expressed in CF lung or pancreatic cells, the expression of the F508del-CFTR protein is significantly increased. Importantly, miR-16 promotes functional rescue of the cyclic AMP-activated apical F508del-CFTR chloride channel in primary lung epithelial cells from CF patients. We interpret these findings to suggest that these miRs may constitute novel targets for CF therapy.

Indexed as

Cell LineCells, CulturedCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorEpithelial CellsGenetic TherapyHumansMicroRNAsMutationRespiratory MucosaRNA, MessengerCFTR protein, humanCystic Fibrosis Transmembrane Conductance RegulatorMicroRNAsMIRN16 microRNA, humanRNA, Messenger

Identifiers

PMID26133785
PMCPMC5488273
OpenAlexW1710864732

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.