Evidence map›Paper›PMID 24901050›Full record

ArticleCell death & disease2014

miR-125b controls apoptosis and temozolomide resistance by targeting TNFAIP3 and NKIRAS2 in glioblastomas.

S Haemmig, U Baumgartner, A Glück, S Zbinden, M P Tschan, A Kappeler, L Mariani, I Vajtai, E Vassella

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

Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed, 3 pooled it
2.3field-weighted citation impact, top 12% 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

52 citing papers in PubMed, 3 syntheses or guidelines pooled it, 92 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. MIR4726Cell communication and signaling : CCS · 2025
    Article
  12. Review
  13. Review
  14. Review
  15. Article
  16. Article
  17. Review
  18. Review
  19. Article
  20. 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

9 authors at 2 institutions in 1 country.

S HaemmigInstitut für Pathologie, University of Bern, Bern, Switzerland.
U BaumgartnerInstitut für Pathologie, University of Bern, Bern, Switzerland.
A GlückInstitut für Pathologie, University of Bern, Bern, Switzerland.
S ZbindenInstitut für Pathologie, University of Bern, Bern, Switzerland.
M P TschanInstitut für Pathologie, University of Bern, Bern, Switzerland.
A KappelerInstitut für Pathologie, University of Bern, Bern, Switzerland.
L MarianiKlinik und Poliklinik, University Hospital Basel, Basel, Switzerland.
I VajtaiInstitut für Pathologie, University of Bern, Bern, Switzerland.
E VassellaInstitut für Pathologie, University of Bern, Bern, Switzerland.
University of Bern · CHUniversity Hospital of Basel · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Diffusely infiltrating gliomas are among the most prognostically discouraging neoplasia in human. Temozolomide (TMZ) in combination with radiotherapy is currently used for the treatment of glioblastoma (GBM) patients, but less than half of the patients respond to therapy and chemoresistance develops rapidly. Epigenetic silencing of the O(6)-methylguanine-DNA methyltransferase (MGMT) has been associated with longer survival in GBM patients treated with TMZ, but nuclear factor κB (NF-κB)-mediated survival signaling and TP53 mutations contribute significantly to TMZ resistance. Enhanced NF-κB is in part owing to downregulation of negative regulators of NF-κB activity, including Tumor necrosis factor alpha-induced protein 3 (TNFAIP3) and NF-κB inhibitor interacting RAS-like 2 (NKIRAS2). Here we provide a novel mechanism independent of TP53 and MGMT by which oncogenic miR-125b confers TMZ resistance by targeting TNFAIP3 and NKIRAS2. GBM cells overexpressing miR-125b showed increased NF-κB activity and upregulation of anti-apoptotic and cell cycle genes. This was significantly associated with resistance of GBM cells to TNFα- and TNF-related inducing ligand-induced apoptosis as well as resistance to TMZ. Conversely, overexpression of anti-miR-125b resulted in cell cycle arrest, increased apoptosis and increased sensitivity to TMZ, indicating that endogenous miR-125b is sufficient to control these processes. GBM cells overexpressing TNFAIP3 and NKIRAS2 were refractory to miR-125b-induced apoptosis resistance as well as TMZ resistance, indicating that both genes are relevant targets of miR-125b. In GBM tissues, high miR-125b expression was significantly correlated with nuclear NF-κB confirming that miR-125b is implicated in NF-κB signaling. Most remarkably, miR-125b overexpression was clearly associated with shorter overall survival of patients treated with TMZ, suggesting that this microRNA is an important predictor of response to therapy.

Indexed as

ApoptosisDrug Resistance, NeoplasmCell Line, TumorDacarbazineDNA-Binding ProteinsGlioblastomaHumansIntracellular Signaling Peptides and ProteinsMicroRNAsNuclear Proteinsras ProteinsRNA, NeoplasmTemozolomideTumor Necrosis Factor alpha-Induced Protein 3DacarbazineDNA-Binding ProteinsIntracellular Signaling Peptides and ProteinsMicroRNAsMIRN125 microRNA, humanNuclear Proteinsras ProteinsRNA, NeoplasmTemozolomideTNFAIP3 protein, humanTumor Necrosis Factor alpha-Induced Protein 3

Identifiers

PMID24901050
PMCPMC4611719
OpenAlexW1984386151

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.