Evidence map›Paper›PMID 23974981›Full record

ArticleLeukemia2014

Defective DROSHA processing contributes to downregulation of MiR-15/-16 in chronic lymphocytic leukemia.

D Allegra, V Bilan, A Garding, H Döhner, S Stilgenbauer, F Kuchenbauer, D Mertens, M Zucknick

Erratum issuedAbstract read
PubMed Publisher
In one paragraph

Article in Leukemia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 44 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed, 1 pooled it
2.0field-weighted citation impact, top 14% 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

44 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Review
  6. Review
  7. Article
  8. Review
  9. Role of microRNAs in Chronic Lymphocytic Leukemia.International journal of molecular sciences · 2023
    Review
  10. Review
  11. Article
  12. Review
  13. Review
  14. Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Targeting microRNA in hematologic malignancies.Current opinion in oncology · 2020
    Review
  20. Review
4 · The record

Corrections and comments

  • Erratum issued
    Zucknick, Manuela [Added]
5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

D Allegra1] Department of Internal Medicine III, Ulm University, Ulm, Germany [2] Cooperation Unit 'Mechanisms of Leukemogenesis', German Cancer Research Center DKFZ, Heidelberg, Germany.
V BilanDepartment of Internal Medicine III, Ulm University, Ulm, Germany.
A Garding1] Department of Internal Medicine III, Ulm University, Ulm, Germany [2] Signalling to Chromatin Laboratory, Institute of Molecular Biology, Mainz, Germany.
H DöhnerDepartment of Internal Medicine III, Ulm University, Ulm, Germany.
S StilgenbauerDepartment of Internal Medicine III, Ulm University, Ulm, Germany.
F KuchenbauerDepartment of Internal Medicine III, Ulm University, Ulm, Germany.
D Mertens1] Department of Internal Medicine III, Ulm University, Ulm, Germany [2] Cooperation Unit 'Mechanisms of Leukemogenesis', German Cancer Research Center DKFZ, Heidelberg, Germany.
M Zucknick
Universität Ulm · DEHeidelberg University · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The MIR-15A/-16-1 tumor suppressor microRNAs (miRNAs) are deleted in leukemic cells from more than 50% of patients with chronic lymphocytic leukemia (CLL). As these miRNAs are also less abundant in patients without genomic deletion, their downregulation in CLL is likely to be caused by additional mechanisms. We found the primary transcripts (pri-miRNAs) of MIR-15a/-16/-15b to be elevated and processing intermediates (precursor miRNAs) to be reduced in cells from CLL patients (22/38) compared with non-malignant B-cells (n=14), indicating a block of miRNA maturation at the DROSHA processing step. Using a luciferase reporter assay for pri-miR processing we validated the defect in primary CLL cells. The block of miRNA maturation is restricted to specific miRNAs and can be found in the cell line MEC-2, but not in MEC-1, even though both are derived from the same CLL patient. In these cells, the RNA-specific deaminase ADARB1 leads to reduced pri-miRNA processing, but full processing efficiency is recovered upon deletion of the RNA-binding domains or nuclear localization of ADARB1. Thus, we show that, apart from genomic deletion or transcriptional downregulation, aberrant processing of miRNA leads to specific reduction of miRNAs in leukemic cells. This represents a novel oncogenic mechanism in the pathogenesis of CLL.

Indexed as

Down-RegulationAdenosine Deaminasebeta CateninCell Line, TumorHumansLeukemia, Lymphocytic, Chronic, B-CellMicroRNAsProtein Processing, Post-TranslationalRibonuclease IIIRNA-Binding ProteinsADARB1 protein, humanAdenosine Deaminasebeta CateninDROSHA protein, humanMicroRNAsRibonuclease IIIRNA-Binding Proteins

Identifiers

PMID23974981
OpenAlexW2037980270

What OpenQuestion holds

Textmetadata
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.