Evidence map›Paper›PMID 25898773›Full record

ArticleMolecular oncology2015

miRNA-221 and miRNA-222 induce apoptosis via the KIT/AKT signalling pathway in gastrointestinal stromal tumours.

Michaela Angelika Ihle, Marcel Trautmann, Helen Kuenstlinger, Sebastian Huss, Carina Heydt, Jana Fassunke, Eva Wardelmann, Sebastian Bauer, Hans-Ulrich Schildhaus, Reinhard Buettner and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Molecular oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
9.9field-weighted citation impact, top 1% 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

51 citing papers in PubMed, 88 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Review
  6. MiR-582 Down-Regulates Lissencephaly-1 (Iranian journal of biotechnology · 2022
    Article
  7. Article
  8. Review
  9. Article
  10. Noncoding RNAs in Drug Resistance of Gastrointestinal Stromal Tumor.Frontiers in cell and developmental biology · 2022
    Review
  11. Article
  12. Article
  13. Review
  14. Signaling Modulation byFrontiers in cell and developmental biology · 2021
    Article
  15. Article
  16. Prognostic Impact ofCancers · 2020
    Article
  17. Review
  18. Review
  19. The Role of miR-375-3p and miR-200b-3p in Gastrointestinal Stromal Tumors.International journal of molecular sciences · 2020
    Article
  20. Article
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.

Michaela Angelika IhleInstitute of Pathology, University of Cologne, Medical Centre, Cologne, Germany. Electronic address: michaela.ihle@uk-koeln.de.
Marcel TrautmannInstitute of Pathology, University of Cologne, Medical Centre, Cologne, Germany.
Helen KuenstlingerInstitute of Pathology, University of Cologne, Medical Centre, Cologne, Germany.
Sebastian HussInstitute of Pathology, University of Cologne, Medical Centre, Cologne, Germany.
Carina HeydtInstitute of Pathology, University of Cologne, Medical Centre, Cologne, Germany.
Jana FassunkeInstitute of Pathology, University of Cologne, Medical Centre, Cologne, Germany.
Eva WardelmannInstitute of Pathology, University of Cologne, Medical Centre, Cologne, Germany.
Sebastian BauerSarcoma Centre, West German Cancer Centre, University of Essen, Essen, Germany.
Hans-Ulrich SchildhausInstitute of Pathology, University of Cologne, Medical Centre, Cologne, Germany.
Reinhard BuettnerInstitute of Pathology, University of Cologne, Medical Centre, Cologne, Germany.
Sabine Merkelbach-BruseInstitute of Pathology, University of Cologne, Medical Centre, Cologne, Germany.
University of Cologne · DEWest German Heart and Vascular Center Essen · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Aberrantly expressed microRNAs (miRNAs) are involved in many diseases including cancer. In gastrointestinal stromal tumours (GISTs) expression of miR-221 and miR-222 is reduced compared to control tissue and other sarcomas but the functional effects of this downregulation are not fully understood. This study aimed at evaluating the miR-221 and miR-222 expression profiles in different GIST subtypes and the functional role of these miRNAs. Expression of miR-221 and miR-222 was analysed in six KIT exon 9 and three KIT exon 11 mutated and nine wildtype GISTs by qPCR. Viability and apoptosis were examined in three different, KIT positive GIST cell lines (GIST882, GIST-T1 and GIST48) after overexpression of these miRNAs. The modulation of KIT and the PI3K/AKT pathways was determined by Western blot. Wildtype and KIT mutated GISTs revealed reduced miRNA expression compared to adequate control tissue. miRNA expression was lower for wildtype compared to mutated GISTs. Transient transfection of miR-221 and miR-222 reduced viability and induced apoptosis by inhibition of KIT expression and its phosphorylation and activation of caspases 3 and 7 in all three GIST cell lines. p-AKT, AKT and BCL2 expression was reduced after miRNA transfection whereas only slight influence on p-MTOR, MTOR and BCL2L11 (BIM) was detected. Our results demonstrate that miR-221 and miR-222 which are downregulated in wildtype and mutated GISTs, induce apoptosis in vitro by a signalling cascade involving KIT, AKT and BCL2. Therefore, overexpression of these miRNAs seems to functionally counteract oncogenic signalling pathways in GIST.

Indexed as

Signal TransductionApoptosisCell Line, TumorGastrointestinal Stromal TumorsHumansMicroRNAsProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-kitMicroRNAsMIR221, humanMIR222, humanProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-kitApoptosisExpressionGISTKITmiR-221miR-222

Identifiers

PMID25898773
PMCPMC5528808
OpenAlexW2148855188

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.