Evidence map›Paper›PMID 30654190›Full record

ArticleMolecular therapy. Nucleic acids2019

Activating PTEN Tumor Suppressor Expression with the CRISPR/dCas9 System.

Colette Moses, Fiona Nugent, Charlene Babra Waryah, Benjamin Garcia-Bloj, Alan R Harvey, Pilar Blancafort

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

Article in Molecular therapy. Nucleic acids, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
3.2field-weighted citation impact, top 7% 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

58 citing papers in PubMed, 135 citations in OpenAlex.

  1. Review
  2. Advances and clinical potential of epigenome editing.Cellular and molecular life sciences : CMLS · 2026
    Review
  3. Article
  4. Review
  5. The Roles of PTEN in Melanoma Suppression.Pigment cell & melanoma research · 2025
    Review
  6. Review
  7. Review
  8. Review
  9. Review
  10. Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. Review
  18. Review
  19. 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

6 authors at 3 institutions in 2 countries.

Colette MosesCancer Epigenetics Laboratory, The Harry Perkins Institute of Medical Research, 6 Verdun Street, Nedlands, WA 6009, Australia; School of Human Sciences, Faculty of Science, The University of Western Australia, 35 Stirling Highway, Perth, WA 6009, Australia.
Fiona NugentCancer Epigenetics Laboratory, The Harry Perkins Institute of Medical Research, 6 Verdun Street, Nedlands, WA 6009, Australia; School of Molecular Sciences, Faculty of Science, The University of Western Australia, 35 Stirling Highway, Perth, WA 6009, Australia.
Charlene Babra WaryahCancer Epigenetics Laboratory, The Harry Perkins Institute of Medical Research, 6 Verdun Street, Nedlands, WA 6009, Australia.
Benjamin Garcia-BlojCancer Epigenetics Laboratory, The Harry Perkins Institute of Medical Research, 6 Verdun Street, Nedlands, WA 6009, Australia; School of Medicine, Faculty of Science, Universidad Mayor, Camino la Piramide 5750, Huechuraba 8580745, Santiago, Chile.
Alan R HarveySchool of Human Sciences, Faculty of Science, The University of Western Australia, 35 Stirling Highway, Perth, WA 6009, Australia; Perron Institute for Neurological and Translational Science, 8 Verdun Street, Nedlands, WA 6009, Australia.
Pilar BlancafortCancer Epigenetics Laboratory, The Harry Perkins Institute of Medical Research, 6 Verdun Street, Nedlands, WA 6009, Australia; School of Human Sciences, Faculty of Science, The University of Western Australia, 35 Stirling Highway, Perth, WA 6009, Australia. Electronic address: pilar.blancafort@uwa.edu.au.
Harry Perkins Institute of Medical Research · AUUniversity of Western Australia · AUUniversidad Mayor · CL

Funding

Targeted epigenetic silencing of oncogenic Transcription Factors (PQ18)R01CA170370 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BLANCAFORT, PILAR · 2012 to 2015
$900k
Precision engineering of DNA methylation patterns in the human genomeR01DA036906 · NIDA · UNIVERSITY OF WESTERN AUSTRALIA · PI BLANCAFORT, PILAR, LISTER, RYAN · 2013 to 2014
$350k
NCI NIH HHS R01 CA170370NIDA NIH HHS R01 DA036906
6 · The paper itself

Abstract

PTEN expression is lost in many cancers, and even small changes in PTEN activity affect susceptibility and prognosis in a range of highly aggressive malignancies, such as melanoma and triple-negative breast cancer (TNBC). Loss of PTEN expression occurs via multiple mechanisms, including mutation, transcriptional repression and epigenetic silencing. Transcriptional repression of PTEN contributes to resistance to inhibitors used in the clinic, such as B-Raf inhibitors in BRAF mutant melanoma. We aimed to activate PTEN expression using the CRISPR system, specifically dead (d) Cas9 fused to the transactivator VP64-p65-Rta (VPR). dCas9-VPR was directed to the PTEN proximal promoter by single-guide RNAs (sgRNAs), in cancer cells that exhibited low levels of PTEN expression. The dCas9-VPR system increased PTEN expression in melanoma and TNBC cell lines, without transcriptional regulation at predicted off-target sgRNA binding sites. PTEN activation significantly repressed downstream oncogenic pathways, including AKT, mTOR, and MAPK signaling. BRAF V600E mutant melanoma cells transduced with dCas9-VPR displayed reduced migration, as well as diminished colony formation in the presence of B-Raf inhibitors, PI3K/mTOR inhibitors, and with combined PI3K/mTOR and B-Raf inhibition. CRISPR-mediated targeted activation of PTEN may provide an alternative therapeutic approach for highly aggressive cancers that are refractory to current treatments.

Indexed as

breast neoplasmsCRISPR/Cas systemshuman PTEN proteinmelanomatumor suppressor genes

Identifiers

PMID30654190
PMCPMC6348769
OpenAlexW2904029973

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.