Evidence map›Paper›PMID 24994119›Full record

ArticleOncotarget2014

A genome-wide miRNA screen revealed miR-603 as a MGMT-regulating miRNA in glioblastomas.

Deepa Kushwaha, Valya Ramakrishnan, Kimberly Ng, Tyler Steed, Thien Nguyen, Diahnn Futalan, Johnny C Akers, Jann Sarkaria, Tao Jiang, Dipanjan Chowdhury and 2 more

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 1 pooled it
4.2field-weighted citation impact, top 5% 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

46 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Role of non-coding RNAs in OOncology letters · 2026
    Review
  4. Article
  5. Review
  6. Review
  7. Genomic Space ofInternational journal of molecular sciences · 2021
    Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Review
  19. Alkylating anticancer agents and their relations to microRNAs.Cancer drug resistance (Alhambra, Calif.) · 2019
    Review
  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

12 authors at 5 institutions in 2 countries.

Deepa KushwahaDept. of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA; These authors contributed equally as first authors.
Valya RamakrishnanCenter for Theoretical and Applied Neuro-Oncology, Moores Cancer Center, Division of Neurosurgery, University of California San Diego, San Diego, CA. These authors contributed equally as first authors.
Kimberly NgDept. of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA.
Tyler SteedCenter for Theoretical and Applied Neuro-Oncology, Moores Cancer Center, Division of Neurosurgery, University of California San Diego, San Diego, CA.
Thien NguyenCenter for Theoretical and Applied Neuro-Oncology, Moores Cancer Center, Division of Neurosurgery, University of California San Diego, San Diego, CA.
Diahnn FutalanCenter for Theoretical and Applied Neuro-Oncology, Moores Cancer Center, Division of Neurosurgery, University of California San Diego, San Diego, CA.
Johnny C AkersCenter for Theoretical and Applied Neuro-Oncology, Moores Cancer Center, Division of Neurosurgery, University of California San Diego, San Diego, CA.
Jann SarkariaMayo Clinic, Department of Radiation Oncology, Rochester, MN.
Tao JiangDepartment of Neurosurgery, Tiantan Medical Center, Beijing, China.
Dipanjan ChowdhuryDept. of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA.
Bob S CarterCenter for Theoretical and Applied Neuro-Oncology, Moores Cancer Center, Division of Neurosurgery, University of California San Diego, San Diego, CA.
Clark C ChenCenter for Theoretical and Applied Neuro-Oncology, Moores Cancer Center, Division of Neurosurgery, University of California San Diego, San Diego, CA.
University of California, San Diego · USDana-Farber Cancer Institute · USCenter for Theoretical Biological Physics · USBeijing Tian Tan Hospital · CNMayo Clinic in Arizona · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007198 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHI, NEIL C, INSEL, PAUL A · 1985 to 2024
$29.3M
Serum microRNA as biomarker for radiation injury to lung and hematopoietic cellsR01AI101897 · NIAID · DANA-FARBER CANCER INST · PI CHOWDHURY, DIPANJAN · 2012 to 2016
$2.1M
NIAID NIH HHS R01 AI101897NIGMS NIH HHS T32 GM007198
6 · The paper itself

Abstract

MGMT expression is a critical determinant for therapeutic resistance to DNA alkylating agents. We previously demonstrated that MGMT expression is post-transcriptionally regulated by miR-181d and other miRNAs. Here, we performed a genome-wide screen to identify MGMT regulating miRNAs. Candidate miRNAs were further tested for inverse correlation with MGMT expression in clinical specimens. We identified 15 candidate miRNAs and characterized the top candidate, miR-603. Transfection of miR-603 suppressed MGMT mRNA/protein expression in vitro and in vivo; this effect was reversed by transfection with antimiR-603. miR-603 affinity-precipitated with MGMT mRNA and suppressed luciferase activity in an MGMT-3'UTR-luciferase assay, suggesting direct interaction between miR-603 and MGMT 3'UTR. miR-603 transfection enhanced the temozolomide (TMZ) sensitivity of MGMT-expressing glioblastoma cell lines. Importantly, miR-603 mediated MGMT suppression and TMZ resistance were reversed by expression of an MGMT cDNA. In a collection of 74 clinical glioblastoma specimens, both miR-603 and miR-181d levels inversely correlated with MGMT expression. Moreover, a combined index of the two miRNAs better reflected MGMT expression than each individually. These results suggest that MGMT is co-regulated by independent miRNAs. Characterization of these miRNAs should contribute toward strategies for enhancing the efficacy of DNA alkylating agents.

Indexed as

Biomarkers, TumorBrain NeoplasmsCell ProliferationDNA Modification MethylasesDNA Repair EnzymesGene Expression Regulation, NeoplasticGlioblastomaHumansMicroRNAsPrognosisTransfectionTumor Suppressor ProteinsBiomarkers, TumorDNA Modification MethylasesDNA Repair EnzymesMGMT protein, humanMicroRNAsTumor Suppressor Proteins

Identifiers

PMID24994119
PMCPMC4147303
OpenAlexW1916931627

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.