Evidence map›Paper›PMID 35269443›Full record

ArticleCells2022

miRNA-Dependent Regulation of AKT1 Phosphorylation.

Mallory I Frederick, Tarana Siddika, Pengcheng Zhang, Nileeka Balasuriya, Matthew A Turk, Patrick O'Donoghue, Ilka U Heinemann

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

Article in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

19 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Exploration of the Mechanisms ofCurrent issues in molecular biology · 2025
    Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. 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 1 institution in 1 country.

Mallory I FrederickDepartment of Biochemistry, The University of Western Ontario, 1151 Richmond Street, London, ON N6A 5C1, Canada.
Tarana SiddikaDepartment of Biochemistry, The University of Western Ontario, 1151 Richmond Street, London, ON N6A 5C1, Canada.
Pengcheng ZhangDepartment of Biochemistry, The University of Western Ontario, 1151 Richmond Street, London, ON N6A 5C1, Canada.ORCID 0000-0001-6945-309X
Nileeka BalasuriyaDepartment of Biochemistry, The University of Western Ontario, 1151 Richmond Street, London, ON N6A 5C1, Canada.
Matthew A TurkDepartment of Biochemistry, The University of Western Ontario, 1151 Richmond Street, London, ON N6A 5C1, Canada.ORCID 0000-0001-9806-9644
Patrick O'DonoghueDepartment of Biochemistry, The University of Western Ontario, 1151 Richmond Street, London, ON N6A 5C1, Canada.
Ilka U HeinemannDepartment of Biochemistry, The University of Western Ontario, 1151 Richmond Street, London, ON N6A 5C1, Canada.
Western University · CA

Funding

Canada Foundation for Innovation 229917Canada Research Chairs Program 232341CIHR 165985Natural Sciences and Engineering Research Council 04282-2014Natural Sciences and Engineering Research Council 04776-2014Ontario Ministry of Research and Innovation ER-18-14-183Ontario Research Fund 229917
6 · The paper itself

Abstract

The phosphoinositide-3-kinase (PI3K)/AKT pathway regulates cell survival and is over-activated in most human cancers, including ovarian cancer. Following growth factor stimulation, AKT1 is activated by phosphorylation at T308 and S473. Disruption of the AKT1 signaling pathway is sufficient to inhibit the epithelial-mesenchymal transition in epithelial ovarian cancer (EOC) cells. In metastatic disease, adherent EOC cells transition to a dormant spheroid state, characterized previously by low S473 phosphorylation in AKT1. We confirmed this finding and observed that T308 phosphorylation was yet further reduced in EOC spheroids and that the transition from adherent to spheroid growth is accompanied by significantly increased levels of let-7 miRNAs. We then used mechanistic studies to investigate the impact of let-7 miRNAs on AKT1 phosphorylation status and activity in cells. In growth factor-stimulated HEK 293T cells supplemented with let-7a, we found increased phosphorylation of AKT1 at T308, decreased phosphorylation at S473, and enhanced downstream AKT1 substrate GSK-3β phosphorylation. Let-7b and let-7g also deregulated AKT signaling by rendering AKT1 insensitive to growth factor simulation. We uncovered let-7a-dependent deregulation of PI3K pathway components, including PI3KC2A, PDK1, and RICTOR, that govern AKT1 phosphorylation and activity. Together, our data show a new role for miRNAs in regulating AKT signaling.

Indexed as

MicroRNAsOvarian NeoplasmsCarcinoma, Ovarian EpithelialGlycogen Synthase Kinase 3 betaHumansPhosphatidylinositol 3-KinasesPhosphorylationProto-Oncogene Proteins c-aktAKT1 protein, humanGlycogen Synthase Kinase 3 betaMicroRNAsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktmiRNAoncogenic kinaseposttranslational modificationprotein phosphorylationsignaling

Identifiers

PMID35269443
PMCPMC8909289
OpenAlexW4214777037

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.