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P16-specific DNA methylation by engineered zinc finger methyltransferase inactivates gene transcription and promotes cancer metastasis

Overview of attention for article published in Genome Biology, November 2015
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  • Good Attention Score compared to outputs of the same age (76th percentile)

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Title
P16-specific DNA methylation by engineered zinc finger methyltransferase inactivates gene transcription and promotes cancer metastasis
Published in
Genome Biology, November 2015
DOI 10.1186/s13059-015-0819-6
Pubmed ID
Authors

Chenghua Cui, Ying Gan, Liankun Gu, James Wilson, Zhaojun Liu, Baozhen Zhang, Dajun Deng

Abstract

P16 DNA methylation is well known to be the most frequent event in cancer development. It has been reported that genetic inactivation of P16 drives cancer growth and metastasis, however, whether P16 DNA methylation is truly a driver in cancer metastasis remains unknown. A P16-specific DNA methyltransferase (P16-dnmt) expression vector is designed using a P16 promoter-specific engineered zinc finger protein fused with the catalytic domain of dnmt3a. P16-dnmt transfection significantly decreases P16 promoter activity, induces complete methylation of P16 CpG islands, and inactivates P16 transcription in the HEK293T cell line. The P16-Dnmt coding fragment is integrated into an expression controllable vector and used to induce P16-specific DNA methylation in GES-1 and BGC823 cell lines. Transwell assays show enhanced migration and invasion of these cancer cells following P16-specific DNA methylation. Such effects are not observed in the P16 mutant A549 cell line. These results are confirmed using an experimental mouse pneumonic metastasis model. Moreover, enforced overexpression of P16 in these cells reverses the migration phenotype. Increased levels of RB phosphorylation and NFκB subunit P65 expression are also seen following P16-specific methylation and might further contribute to cancer metastasis. P16 methylation could directly inactivate gene transcription and drive cancer metastasis.

X Demographics

X Demographics

The data shown below were collected from the profiles of 7 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 57 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Russia 1 2%
China 1 2%
Unknown 55 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 15 26%
Student > Bachelor 7 12%
Student > Master 6 11%
Researcher 5 9%
Student > Postgraduate 4 7%
Other 12 21%
Unknown 8 14%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 20 35%
Agricultural and Biological Sciences 15 26%
Medicine and Dentistry 3 5%
Neuroscience 3 5%
Pharmacology, Toxicology and Pharmaceutical Science 1 2%
Other 5 9%
Unknown 10 18%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 6. 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 06 July 2016.
All research outputs
#6,443,957
of 25,374,917 outputs
Outputs from Genome Biology
#3,088
of 4,467 outputs
Outputs of similar age
#90,326
of 393,297 outputs
Outputs of similar age from Genome Biology
#61
of 72 outputs
Altmetric has tracked 25,374,917 research outputs across all sources so far. This one has received more attention than most of these and is in the 74th percentile.
So far Altmetric has tracked 4,467 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 27.6. This one is in the 30th percentile – i.e., 30% of its peers scored the same or lower than it.
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 393,297 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 76% of its contemporaries.
We're also able to compare this research output to 72 others from the same source and published within six weeks on either side of this one. This one is in the 15th percentile – i.e., 15% of its contemporaries scored the same or lower than it.