Evidence map›Paper›PMID 26464442›Full record

ArticleNucleic acids research2015

Perturbations of PIP3 signalling trigger a global remodelling of mRNA landscape and reveal a transcriptional feedback loop.

Vladimir Yu Kiselev, Veronique Juvin, Mouhannad Malek, Nicholas Luscombe, Phillip Hawkins, Nicolas Le Novère, Len Stephens

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
0.8field-weighted citation impact, top 27% 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

16 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Deriving Ranges of Optimal Estimated Transcript Expression due to Nonidentifiability.Journal of computational biology : a journal of computational molecular cell biology · 2022
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. OncogenicProceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  12. Article
  13. Article
  14. PTEN Regulates PI(3,4)PMolecular cell · 2017
    Article
  15. Article
  16. 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

7 authors at 2 institutions in 1 country.

Vladimir Yu KiselevBabraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK.
Veronique JuvinBabraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK.
Mouhannad MalekBabraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK.
Nicholas LuscombeLondon Research Institute, London, WC2A 3LY, UK.
Phillip HawkinsBabraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK.
Nicolas Le NovèreBabraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK EMBL-European Bioinformatics Institute, Hinxton, CB10 1SD, UK lenov@babraham.ac.uk.
Len StephensBabraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK.
Babraham Institute · GBEuropean Bioinformatics Institute · GB

Funding

Biotechnology and Biological Sciences Research Council BB/I003428Biotechnology and Biological Sciences Research Council BBS/E/B/0000S239Biotechnology and Biological Sciences Research Council BBS/E/B/000C0413Biotechnology and Biological Sciences Research Council BBS/E/B/000C0417Biotechnology and Biological Sciences Research Council BBS/E/B/000C0419
6 · The paper itself

Abstract

PIP3 is synthesized by the Class I PI3Ks and regulates complex cell responses, such as growth and migration. Signals that drive long-term reshaping of cell phenotypes are difficult to resolve because of complex feedback networks that operate over extended times. PIP3-dependent modulation of mRNA accumulation is clearly important in this process but is poorly understood. We have quantified the genome-wide mRNA-landscape of non-transformed, breast epithelium-derived MCF10a cells and its response to acute regulation by EGF, in the presence or absence of a PI3Kα inhibitor, compare it to chronic activation of PI3K signalling by cancer-relevant mutations (isogenic cells expressing an oncomutant PI3Kα allele or lacking the PIP3-phosphatase/tumour-suppressor, PTEN). Our results show that whilst many mRNAs are changed by long-term genetic perturbation of PIP3 signalling ('butterfly effect'), a much smaller number do so in a coherent fashion with the different PIP3 perturbations. This suggests a subset of more directly regulated mRNAs. We show that mRNAs respond differently to given aspects of PIP3 regulation. Some PIP3-sensitive mRNAs encode PI3K pathway components, thus suggesting a transcriptional feedback loop. We identify the transcription factor binding motifs SRF and PRDM1 as important regulators of PIP3-sensitive mRNAs involved in cell movement.

Indexed as

Gene Expression RegulationTranscription, GeneticBreastCell LineClass I Phosphatidylinositol 3-KinasesEpidermal Growth FactorFeedback, PhysiologicalFemaleHumansMutationNucleotide MotifsPhosphatidylinositol 3-KinasesPhosphatidylinositol PhosphatesPTEN PhosphohydrolaseRNA, MessengerSignal TransductionClass I Phosphatidylinositol 3-KinasesEpidermal Growth Factorphosphatidylinositol 3,4,5-triphosphatePhosphatidylinositol 3-KinasesPhosphatidylinositol PhosphatesPIK3CA protein, humanPTEN PhosphohydrolasePTEN protein, humanRNA, MessengerTranscription Factors

Identifiers

PMID26464442
PMCPMC4787766
OpenAlexW2262923393

What Socratic 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 Socratic graph.