Evidence map›Paper›PMID 24184504›Full record

ArticleBiochemical pharmacology2014

ABCC4 is regulated by microRNA-124a and microRNA-506.

Svetlana M Markova, Deanna L Kroetz

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

Article in Biochemical pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

25 citing papers in PubMed, 41 citations in OpenAlex.

  1. Article
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  10. Bioengineered Noncoding RNAs Selectively Change Cellular miRNome Profiles for Cancer Therapy.The Journal of pharmacology and experimental therapeutics · 2018
    Article
  11. Article
  12. MiRNAs and miRNA Polymorphisms Modify Drug Response.International journal of environmental research and public health · 2016
    Review
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  15. Article
  16. Article
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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

2 authors at 1 institution in 1 country.

Svetlana M MarkovaDepartment of Bioengineering and Therapeutic Sciences (SMM, DLK) and Institute for Human Genetics (DLK) , 1550 4th Street RH584E, San Francisco, CA 94158-2911, USA.
Deanna L KroetzDepartment of Bioengineering and Therapeutic Sciences (SMM, DLK) and Institute for Human Genetics (DLK) , 1550 4th Street RH584E, San Francisco, CA 94158-2911, USA. Electronic address: deanna.kroetz@ucsf.edu.
University of California, San Francisco · US

Funding

UCSF Liver Core CenterP30DK026743 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Jennifer Y. Chen · 1986 to 2026
$30.7M
PHARMACOGENETICS OF MEMBRANE TRANSPORTERSU01GM061390 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GIACOMINI, KATHLEEN M · 2000 to 2009
$29.2M
Pharmacogenomics of Membrane TransportersU19GM061390 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YEE, SOOK WAH · 2010 to 2014
$16.3M
NIDDK NIH HHS P30 DK026743NIGMS NIH HHS U01 GM061390NIGMS NIH HHS U19 GM061390
6 · The paper itself

Abstract

Multidrug resistance protein 4 (MRP4, ABCC4) is an efflux membrane transporter expressed in renal tubules, hepatocytes, brain capillaries, prostate and blood cells. MRP4 drives energy dependent efflux of important physiological and pharmacological compounds. MRP4 expression and function is highly variable but cannot be fully attributed to known mechanisms. The goal of this study was to characterize ABCC4 regulation by miRNAs and to assess the influence of ABCC4 3'-UTR polymorphisms on ABCC4 regulation by miRNAs. miR-124a and miR-506 decreased MRP4 protein levels in HEK293T/17 cells 20-30% and MRP4 function by 50%. These miRNAs did not affect ABCC4 mRNA expression. Moreover, miR-124a and miR-506 expression was negatively correlated with MRP4 protein expression in 26 human kidney samples (Spearman r=-0.62, P=0.007 and r=-0.41, P=0.03 for miR-124a and miR-506, respectively). To assess the effect of ABCC4 3'-UTR polymorphisms, six common 3'-UTR haplotypes were inferred in Caucasians, African Americans and Asians and tested in luciferase reporter assays. Multiple ABCC4 3'-UTR haplotypes caused significant reductions in luciferase activity; in the presence of miR-124a or miR-506 mimics the luciferase activity of all six ABCC4 3'-UTR haplotypes was further reduced. Mutation of the putative binding site for miR-124a and miR-506 in the ABCC4 3'-UTR eliminated the effect of these miRNAs. In conclusion, ABCC4 is directly regulated by miR-124a and miR-506 but polymorphisms in the ABCC4 3'-UTR have no significant effect on this miRNA regulation. Regulation of ABCC4 by miRNAs represents a novel mechanism for regulation of MRP4 function.

Indexed as

ATP-Binding Cassette, Sub-Family C ProteinsComputer SimulationGene Expression RegulationHaplotypesHEK293 CellsHumansKidneyMicroRNAsModels, GeneticPolymorphism, GeneticABCC4 protein, humanATP-Binding Cassette, Sub-Family C ProteinsMicroRNAsMIRN124 microRNA, humanMIRN506 microRNA, humanABCC4(ATP-binding cassette transporter member C4)MCBmicroRNA(monochlorobimane)MRP4Multidrug resistance associated protein(multidrug resistance protein member 4)Polymorphism.

Identifiers

PMID24184504
PMCPMC3927324
OpenAlexW2027388200

What OpenQuestion holds

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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.