Evidence map›Paper›PMID 37120619›Full record

ArticleClinical epigenetics2023

Epigenetic reactivation of tumor suppressor genes with CRISPRa technologies as precision therapy for hepatocellular carcinoma.

Agustin Sgro, Joseph Cursons, Charlene Waryah, Eleanor A Woodward, Momeneh Foroutan, Ruqian Lyu, George C T Yeoh, Peter J Leedman, Pilar Blancafort

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

Article in Clinical epigenetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

14 citing papers in PubMed, 20 citations in OpenAlex.

  1. Review
  2. Advances and clinical potential of epigenome editing.Cellular and molecular life sciences : CMLS · 2026
    Review
  3. Review
  4. Review
  5. Review
  6. Article
  7. Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. CRISPR/Cas9 systems: Delivery technologies and biomedical applications.Asian journal of pharmaceutical sciences · 2023
    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

9 authors at 3 institutions in 1 country.

Agustin SgroCancer Epigenetics Group, The Harry Perkins Institute of Medical Research, Nedlands, Perth, WA, 6009, Australia.ORCID 0000-0003-1230-2623
Joseph CursonsBiomedicine Discovery Institute and the Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, 3800, Australia.ORCID 0000-0002-5053-4540
Charlene WaryahCancer Epigenetics Group, The Harry Perkins Institute of Medical Research, Nedlands, Perth, WA, 6009, Australia.ORCID 0000-0002-1295-320X
Eleanor A WoodwardCancer Epigenetics Group, The Harry Perkins Institute of Medical Research, Nedlands, Perth, WA, 6009, Australia.ORCID 0000-0001-7259-6446
Momeneh ForoutanBiomedicine Discovery Institute and the Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, 3800, Australia.ORCID 0000-0002-1440-0457
Ruqian LyuBioinformatics and Cellular Genomics, St Vincent's Institute of Medical Research, Fitzroy, Melbourne, VIC, 3065, Australia.ORCID 0000-0002-7736-6612
George C T YeohCentre for Medical Research, The University of Western Australia, Perth, WA, 6009, Australia.ORCID 0000-0002-4740-4702
Peter J LeedmanCentre for Medical Research, The University of Western Australia, Perth, WA, 6009, Australia.ORCID 0000-0002-1831-4804
Pilar BlancafortCancer Epigenetics Group, The Harry Perkins Institute of Medical Research, Nedlands, Perth, WA, 6009, Australia. pilar.blancafort@uwa.edu.au.ORCID 0000-0002-3881-7396
The University of Western Australia · AUAustralian Regenerative Medicine Institute · AUThe University of Melbourne · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEpigenetic silencing of tumor suppressor genes (TSGs) is a key feature of oncogenesis in hepatocellular carcinoma (HCC). Liver-targeted delivery of CRISPR-activation (CRISPRa) systems makes it possible to exploit chromatin plasticity, by reprogramming transcriptional dysregulation.

resultsUsing The Cancer Genome Atlas HCC data, we identify 12 putative TSGs with negative associations between promoter DNA methylation and transcript abundance, with limited genetic alterations. All HCC samples harbor at least one silenced TSG, suggesting that combining a specific panel of genomic targets could maximize efficacy, and potentially improve outcomes as a personalized treatment strategy for HCC patients. Unlike epigenetic modifying drugs lacking locus selectivity, CRISPRa systems enable potent and precise reactivation of at least 4 TSGs tailored to representative HCC lines. Concerted reactivation of HHIP, MT1M, PZP, and TTC36 in Hep3B cells inhibits multiple facets of HCC pathogenesis, such as cell viability, proliferation, and migration.

conclusionsBy combining multiple effector domains, we demonstrate the utility of a CRISPRa toolbox of epigenetic effectors and gRNAs for patient-specific treatment of aggressive HCC.

Indexed as

Carcinoma, HepatocellularLiver NeoplasmsCell Line, TumorClustered Regularly Interspaced Short Palindromic RepeatsDNA MethylationEpigenesis, GeneticGene Expression Regulation, NeoplasticGenes, Tumor SuppressorHumansCRISPRaEpigenetic drugsEpigenetic editing toolboxGenome multiplexingHepatocellular carcinomaPrecision medicineTumor suppressor genes

Identifiers

PMID37120619
PMCPMC10149030
OpenAlexW4367367507

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.