Evidence map›Paper›PMID 32926965›Full record

ArticleExperimental hematology2020

Metformin-induced suppression of Nemo-like kinase improves erythropoiesis in preclinical models of Diamond-Blackfan anemia through induction of miR-26a.

Mark C Wilkes, Kavitha Siva, Gianluca Varetti, Jacqueline Mercado, Ethan P Wentworth, Cristina A Perez, Mallika Saxena, Sharon Kam, Simryn Kapur, Jun Chen and 6 more

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

Article in Experimental hematology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.6field-weighted citation impact, top 34% 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

8 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Post-transcriptional regulation of erythropoiesis.Blood science (Baltimore, Md.) · 2023
    Review
  6. Diamond-Blackfan anemia.Hematology. American Society of Hematology. Education Program · 2021
    Article
  7. Review
  8. Using the Zebrafish as a Genetic Model to Study Erythropoiesis.International journal of molecular sciences · 2021
    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

16 authors at 5 institutions in 3 countries.

Mark C WilkesDivision of Hematology/Oncology, Department of Pediatrics, Stanford University, Stanford, CA.
Kavitha SivaDepartment of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, Lund, Sweden.
Gianluca VarettiTumour Suppression Group, Spanish National Cancer Research Centre, Madrid, Spain.
Jacqueline MercadoDivision of Hematology/Oncology, Department of Pediatrics, Stanford University, Stanford, CA.
Ethan P WentworthDivision of Hematology/Oncology, Department of Pediatrics, Stanford University, Stanford, CA.
Cristina A PerezDivision of Hematology/Oncology, Department of Pediatrics, Stanford University, Stanford, CA.
Mallika SaxenaDivision of Hematology/Oncology, Department of Pediatrics, Stanford University, Stanford, CA.
Sharon KamDivision of Hematology/Oncology, Department of Pediatrics, Stanford University, Stanford, CA.
Simryn KapurDivision of Hematology/Oncology, Department of Pediatrics, Stanford University, Stanford, CA.
Jun ChenDepartment of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, Lund, Sweden.
Anu NarlaDivision of Hematology/Oncology, Department of Pediatrics, Stanford University, Stanford, CA.
Bert GladerDivision of Hematology/Oncology, Department of Pediatrics, Stanford University, Stanford, CA.
Shou LinDepartment of Molecular, Cell and Development Biology, University of California, Los Angeles, Los Angeles, CA.
Manuel SerranoTumour Suppression Group, Spanish National Cancer Research Centre, Madrid, Spain.
Johan FlygareDepartment of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, Lund, Sweden.
Kathleen M SakamotoDivision of Hematology/Oncology, Department of Pediatrics, Stanford University, Stanford, CA. Electronic address: kmsakamo@stanford.edu.
Stanford University · USLund University · SESpanish National Cancer Research Centre · ESStanford Medicine · USUniversity of California, Los Angeles · US

Funding

Training in Pediatric Nonmalignant Hematology and Stem Cell BiologyT32DK098132 · NIDDK · STANFORD UNIVERSITY · PI SAKAMOTO, KATHLEEN M · 2014 to 2022
$1.9M
Signaling Pathways in MDSR01DK107286 · NIDDK · STANFORD UNIVERSITY · PI SAKAMOTO, KATHLEEN M · 2016 to 2019
$1.4M
Signaling Pathways in MDSR56DK107286 · NIDDK · STANFORD UNIVERSITY · PI LIN, SHUO, SAKAMOTO, KATHLEEN M · 2015 to 2015
$113k
NIDDK NIH HHS R01 DK107286NIDDK NIH HHS R56 DK107286NIDDK NIH HHS T32 DK098132
6 · The paper itself

Abstract

Diamond-Blackfan anemia (DBA) results from haploinsufficiency of ribosomal protein subunits in hematopoietic progenitors in the earliest stages of committed erythropoiesis. Nemo-like kinase (NLK) is chronically hyperactivated in committed erythroid progenitors and precursors in multiple human and murine models of DBA. Inhibition of NLK activity and suppression of NLK expression both improve erythroid expansion in these models. Metformin is a well-tolerated drug for type 2 diabetes with multiple cellular targets. Here we demonstrate that metformin improves erythropoiesis in human and zebrafish models of DBA. Our data indicate that the effects of metformin on erythroid proliferation and differentiation are mediated by suppression of NLK expression through induction of miR-26a, which recognizes a binding site within the NLK 3' untranslated region (3'UTR) to facilitate transcript degradation. We propose that induction of miR-26a is a potentially novel approach to treatment of DBA and could improve anemia in DBA patients without the potentially adverse side effects of metformin in a DBA patient population.

Indexed as

3' Untranslated RegionsAnemia, Diamond-BlackfanAnimalsCells, CulturedColony-Forming Units AssayDisease Models, AnimalErythropoiesisGene Expression RegulationGenes, ReporterHematinicsHumansMetforminMicroRNAsMitogen-Activated Protein KinasesProtein Serine-Threonine KinasesRecombinant Proteins3' Untranslated RegionsHematinicsMetforminMicroRNAsMIRN26 microRNA, humanMirn26 microRNA, mouseMirn26 microRNA, zebrafishMitogen-Activated Protein Kinasesnemo-like kinase, zebrafishNLK protein, humanNlk protein, mouseProtein Serine-Threonine KinasesRecombinant ProteinsRNA, Small Interfering

Identifiers

PMID32926965
PMCPMC8963704
OpenAlexW3086634820

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.