Evidence map›Paper›PMID 37612734›Full record

ArticleClinical epigenetics2023

CRISPR/dCAS9-mediated DNA demethylation screen identifies functional epigenetic determinants of colorectal cancer.

Juan Ramón Tejedor, Alfonso Peñarroya, Javier Gancedo-Verdejo, Pablo Santamarina-Ojeda, Raúl F Pérez, Sara López-Tamargo, Ana Díez-Borge, Juan J Alba-Linares, Nerea González-Del-Rey, Rocío G Urdinguio and 15 more

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 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

11 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Review
  6. Review
  7. Review
  8. Review
  9. Review
  10. Review
  11. 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

25 authors at 9 institutions in 2 countries.

Juan Ramón Tejedor *Nanomaterials and Nanotechnology Research Center (CINN), Spanish National Research Council (CSIC), 33940, El Entrego, Asturias, Spain.
Alfonso Peñarroya *Nanomaterials and Nanotechnology Research Center (CINN), Spanish National Research Council (CSIC), 33940, El Entrego, Asturias, Spain.
Javier Gancedo-VerdejoNanomaterials and Nanotechnology Research Center (CINN), Spanish National Research Council (CSIC), 33940, El Entrego, Asturias, Spain.
Pablo Santamarina-OjedaHealth Research Institute of the Principality of Asturias (ISPA), Avenida de Roma S/N, 33011, Oviedo, Asturias, Spain.
Raúl F PérezNanomaterials and Nanotechnology Research Center (CINN), Spanish National Research Council (CSIC), 33940, El Entrego, Asturias, Spain.
Sara López-TamargoHealth Research Institute of the Principality of Asturias (ISPA), Avenida de Roma S/N, 33011, Oviedo, Asturias, Spain.
Ana Díez-BorgeHealth Research Institute of the Principality of Asturias (ISPA), Avenida de Roma S/N, 33011, Oviedo, Asturias, Spain.
Juan J Alba-LinaresNanomaterials and Nanotechnology Research Center (CINN), Spanish National Research Council (CSIC), 33940, El Entrego, Asturias, Spain.
Nerea González-Del-ReyDepartment of Organisms and Systems Biology, Institute of Biotechnology of Asturias, University of Oviedo, 33071, Oviedo, Asturias, Spain.
Rocío G UrdinguioHealth Research Institute of the Principality of Asturias (ISPA), Avenida de Roma S/N, 33011, Oviedo, Asturias, Spain.
Cristina MangasHealth Research Institute of the Principality of Asturias (ISPA), Avenida de Roma S/N, 33011, Oviedo, Asturias, Spain.
Annalisa RobertiNanomaterials and Nanotechnology Research Center (CINN), Spanish National Research Council (CSIC), 33940, El Entrego, Asturias, Spain.
Virginia LópezHealth Research Institute of the Principality of Asturias (ISPA), Avenida de Roma S/N, 33011, Oviedo, Asturias, Spain.
Teresa Morales-RuizMaimónides Biomedical Research Institute of Córdoba (IMIBIC), 14071, Córdoba, Spain.
Rafael R ArizaMaimónides Biomedical Research Institute of Córdoba (IMIBIC), 14071, Córdoba, Spain.
Teresa Roldán-ArjonaMaimónides Biomedical Research Institute of Córdoba (IMIBIC), 14071, Córdoba, Spain.
Mónica MeijónDepartment of Organisms and Systems Biology, Institute of Biotechnology of Asturias, University of Oviedo, 33071, Oviedo, Asturias, Spain.
Luis ValledorDepartment of Organisms and Systems Biology, Institute of Biotechnology of Asturias, University of Oviedo, 33071, Oviedo, Asturias, Spain.
María Jesús CañalDepartment of Organisms and Systems Biology, Institute of Biotechnology of Asturias, University of Oviedo, 33071, Oviedo, Asturias, Spain.
Daniel Fernández-MartínezHealth Research Institute of the Principality of Asturias (ISPA), Avenida de Roma S/N, 33011, Oviedo, Asturias, Spain.
María Fernández-HeviaHealth Research Institute of the Principality of Asturias (ISPA), Avenida de Roma S/N, 33011, Oviedo, Asturias, Spain.
Paula Jiménez-FonsecaHealth Research Institute of the Principality of Asturias (ISPA), Avenida de Roma S/N, 33011, Oviedo, Asturias, Spain.
Luis J García-FlórezHealth Research Institute of the Principality of Asturias (ISPA), Avenida de Roma S/N, 33011, Oviedo, Asturias, Spain.
Agustín F FernándezNanomaterials and Nanotechnology Research Center (CINN), Spanish National Research Council (CSIC), 33940, El Entrego, Asturias, Spain. agustin.fernandez@cinn.es.
Mario F FragaNanomaterials and Nanotechnology Research Center (CINN), Spanish National Research Council (CSIC), 33940, El Entrego, Asturias, Spain. mffraga@cinn.es.
Universidad de Oviedo · ESGobierno del Principado de Asturias · ESCentre for Biomedical Network Research on Rare Diseases · ESUniversity of Córdoba · ESNanomaterials and Nanotechnology Research Center · ESConsejo Superior de Investigaciones Científicas · ESFernández-Vega Ophthalmological Institute · ESHospital Universitario Central de Asturias · ESPoliclínica Gipuzkoa · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPromoter hypermethylation of tumour suppressor genes is frequently observed during the malignant transformation of colorectal cancer (CRC). However, whether this epigenetic mechanism is functional in cancer or is a mere consequence of the carcinogenic process remains to be elucidated.

resultsIn this work, we performed an integrative multi-omic approach to identify gene candidates with strong correlations between DNA methylation and gene expression in human CRC samples and a set of 8 colon cancer cell lines. As a proof of concept, we combined recent CRISPR-Cas9 epigenome editing tools (dCas9-TET1, dCas9-TET-IM) with a customized arrayed gRNA library to modulate the DNA methylation status of 56 promoters previously linked with strong epigenetic repression in CRC, and we monitored the potential functional consequences of this DNA methylation loss by means of a high-content cell proliferation screen. Overall, the epigenetic modulation of most of these DNA methylated regions had a mild impact on the reactivation of gene expression and on the viability of cancer cells. Interestingly, we found that epigenetic reactivation of RSPO2 in the tumour context was associated with a significant impairment in cell proliferation in p53

conclusionsThese results highlight the potential role of DNA methylation as a driver mechanism of CRC and paves the way for the identification of novel therapeutic windows based on the epigenetic reactivation of certain tumour suppressor genes.

Indexed as

Colonic NeoplasmsDNA MethylationCarcinogenesisDNA DemethylationEpigenesis, GeneticHumansMixed Function OxygenasesProto-Oncogene ProteinsMixed Function OxygenasesProto-Oncogene ProteinsTET1 protein, humanColorectal cancerCRISPR screenDNA methylationEpigeneticsGene expressionTumour suppressor gene

Identifiers

PMID37612734
PMCPMC10464368
OpenAlexW4386116303

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.