Evidence map›Paper›PMID 30991934›Full record

ArticleOpen biology2019

Oncogenic PIK3CA mutations increase dependency on the mRNA cap methyltransferase, RNMT, in breast cancer cells.

Sianadh Dunn, Olivia Lombardi, Radoslaw Lukoszek, Victoria H Cowling

Open access · goldAbstract read
In one paragraph

Article in Open biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
1.0field-weighted citation impact, top 24% 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

26 citing papers in PubMed, 35 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Pan-Cancer Analysis Links Altered RNA mCancer reports (Hoboken, N.J.) · 2024
    Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Review
  20. The potential role of NJournal of hematology & oncology · 2022
    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

4 authors at 1 institution in 1 country.

Sianadh DunnCentre for Gene Regulation and Expression, School of Life Sciences, University of Dundee , Dundee DD1 5EH , UK.
Olivia LombardiCentre for Gene Regulation and Expression, School of Life Sciences, University of Dundee , Dundee DD1 5EH , UK.
Radoslaw LukoszekCentre for Gene Regulation and Expression, School of Life Sciences, University of Dundee , Dundee DD1 5EH , UK.
Victoria H CowlingCentre for Gene Regulation and Expression, School of Life Sciences, University of Dundee , Dundee DD1 5EH , UK.
University of Dundee · GB

Funding

Biotechnology and Biological Sciences Research CouncilMedical Research Council MR/K024213/1Wellcome TrustWellcome Trust 097945/Z/11/ZWellcome Trust 100476/Z/12/Z
6 · The paper itself

Abstract

Basic mechanisms in gene expression are currently being investigated as targets in cancer therapeutics. One such fundamental process is the addition of the cap to pre-mRNA, which recruits mediators of mRNA processing and translation initiation. Maturation of the cap involves mRNA cap guanosine N-7 methylation, catalysed by RNMT (RNA guanine-7 methyltransferase). In a panel of breast cancer cell lines, we investigated whether all are equivalently dependent on RNMT for proliferation. When cellular RNMT activity was experimentally reduced by 50%, the proliferation rate of non-transformed mammary epithelial cells was unchanged, whereas a subset of breast cancer cell lines exhibited reduced proliferation and increased apoptosis. Most of the cell lines which exhibited enhanced dependency on RNMT harboured oncogenic mutations in PIK3CA, which encodes the p110α subunit of PI3Kα. Conversely, all cell lines insensitive to RNMT depletion expressed wild-type PIK3CA. Expression of oncogenic PIK3CA mutants, which increase PI3K p110α activity, was sufficient to increase dependency on RNMT. Conversely, inhibition of PI3Kα reversed dependency on RNMT, suggesting that PI3Kα signalling is required. Collectively, these findings provide evidence to support RNMT as a therapeutic target in breast cancer and suggest that therapies targeting RNMT would be most valuable in a PIK3CA mutant background.

Indexed as

MutationRNA CapsApoptosisBreast NeoplasmsCarcinogenesisCell Line, TumorCell ProliferationClass I Phosphatidylinositol 3-KinasesHumansMCF-7 CellsMethyltransferasesRNA, MessengerSignal TransductionTranscription, GeneticClass I Phosphatidylinositol 3-KinasesMethyltransferasesmRNA (guanine(N7))-methyltransferasePIK3CA protein, humanRNA CapsRNA, Messengerbreast cancercell proliferationmRNA capPI3KαPIK3CARNMT

Identifiers

PMID30991934
PMCPMC6501644
OpenAlexW2938787141

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.