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X Demographics
Mendeley readers
Attention Score in Context
| Title |
CRISPR/dCAS9-mediated DNA demethylation screen identifies functional epigenetic determinants of colorectal cancer
|
|---|---|
| Published in |
Clinical Epigenetics, August 2023
|
| DOI | 10.1186/s13148-023-01546-1 |
| Pubmed ID | |
| Authors |
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, Cristina Mangas, Annalisa Roberti, Virginia López, Teresa Morales-Ruiz, Rafael R. Ariza, Teresa Roldán-Arjona, Mónica Meijón, Luis Valledor, María Jesús Cañal, Daniel Fernández-Martínez, María Fernández-Hevia, Paula Jiménez-Fonseca, Luis J. García-Flórez, Agustín F. Fernández, Mario F. Fraga |
| Abstract |
Promoter 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. In 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-/- cancer cell lines, and further validation with human samples demonstrated that the epigenetic silencing of RSPO2 is a mid-late event in the adenoma to carcinoma sequence. These 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. |
X Demographics
The data shown below were collected from the profiles of 12 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 7 | 58% |
| Unknown | 5 | 42% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 6 | 50% |
| Practitioners (doctors, other healthcare professionals) | 5 | 42% |
| Scientists | 1 | 8% |
Mendeley readers
The data shown below were compiled from readership statistics for 9 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 9 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Unspecified | 1 | 11% |
| Researcher | 1 | 11% |
| Student > Master | 1 | 11% |
| Unknown | 6 | 67% |
| Readers by discipline | Count | As % |
|---|---|---|
| Unspecified | 1 | 11% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 11% |
| Biochemistry, Genetics and Molecular Biology | 1 | 11% |
| Unknown | 6 | 67% |
Attention Score in Context
This research output has an Altmetric Attention Score of 9. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 October 2023.
All research outputs
#4,382,932
of 25,732,188 outputs
Outputs from Clinical Epigenetics
#312
of 1,448 outputs
Outputs of similar age
#68,555
of 358,646 outputs
Outputs of similar age from Clinical Epigenetics
#5
of 39 outputs
Altmetric has tracked 25,732,188 research outputs across all sources so far. Compared to these this one has done well and is in the 82nd percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,448 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.4. This one has done well, scoring higher than 78% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 358,646 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 80% of its contemporaries.
We're also able to compare this research output to 39 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 87% of its contemporaries.