↓ Skip to main content

Induction of active demethylation and 5hmC formation by 5-azacytidine is TET2 dependent and suggests new treatment strategies against hepatocellular carcinoma

Overview of attention for article published in Clinical Epigenetics, September 2015
Altmetric Badge

About this Attention Score

  • Good Attention Score compared to outputs of the same age (66th percentile)

Mentioned by

twitter
6 tweeters

Citations

dimensions_citation
28 Dimensions

Readers on

mendeley
60 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
Induction of active demethylation and 5hmC formation by 5-azacytidine is TET2 dependent and suggests new treatment strategies against hepatocellular carcinoma
Published in
Clinical Epigenetics, September 2015
DOI 10.1186/s13148-015-0133-x
Pubmed ID
Authors

Sahar Olsadat Sajadian, Sabrina Ehnert, Haghighat Vakilian, Eirini Koutsouraki, Georg Damm, Daniel Seehofer, Wolfgang Thasler, Steven Dooley, Hossein Baharvand, Bence Sipos, Andreas K. Nussler

Abstract

Global deregulation of DNA methylation is one of the crucial causes of hepato cellular carcinoma (HCC). It has been reported that the anti-cancer drug 5-azacytidine (5-AZA) mediates the activation of tumor suppressor genes through passive demethylation by inhibiting DNMT1. Recent evidence suggests that active demethylation which is mediated by ten-eleven translocation (TET) proteins may also be an important step to control global methylation. However, there exists a controversial discussion in which TET proteins are involved in the demethylation process in HCC. Therefore, we firstly wanted to identify which of the TETs are involved in demethylation and later to study whether or not 5-AZA could trigger the TET-dependent active demethylation process in HCC. HCC cell lines (Huh-7, HLE, HLF), primary human hepatocytes (hHeps), and tissues from both healthy (55 patients) and HCC patients (55 patients) were included in this study; mRNA levels of isocitrate dehydrogenase (IDH1, 2) and TETs (TET1-3) were studied via qPCR and confirmed by Western blot. The expression of 5hmC/5mC was determined by immunohistochemistry in human HCC tissues and the corresponding adjacent healthy liver. HCC cell lines were stimulated with 5-AZA (0-20 μM) and viability (Resazurin conversion), toxicity (LDH release), proliferation (PCNA), and 5hmC/5mC distribution were assessed. In addition, knockdown experiments on TET proteins in HCC cell lines using short interference RNAs (siRNAs), in the presence and absence of 5-AZA, were performed. Our data applying qPCR, immunofluorescence, and Western blotting clearly show that TET2 and TET3 but not TET1 were significantly decreased in HCC tissue and different HCC cell lines compared to non-tumor liver tissues and hHeps. In addition, we show here for the first time applying knockdown experiments that 5-AZA is able to trigger an active TET2-dependent demethylation process with concomitant significant changes in 5hmC/5mC in HCC cell lines and hHeps. Our data clearly show that the expression and activity of TET2 and TET3 proteins but not TET1 are impaired in hepatocellular carcinoma leading to the reduction of 5hmC in HCCs. Furthermore, this study identified a novel function of 5-azacytidine in promoting a TET-mediated generation of 5hmC suggesting that the availability of 5-AZA in cancer cells will have various effects on different epigenetic targets. These findings may open new therapeutic strategies for epigenetic drugs to treat HCC.

Twitter Demographics

The data shown below were collected from the profiles of 6 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 60 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Iran, Islamic Republic of 1 2%
United States 1 2%
Unknown 58 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 19 32%
Student > Master 12 20%
Researcher 10 17%
Student > Doctoral Student 6 10%
Student > Bachelor 5 8%
Other 7 12%
Unknown 1 2%
Readers by discipline Count As %
Agricultural and Biological Sciences 24 40%
Biochemistry, Genetics and Molecular Biology 21 35%
Medicine and Dentistry 6 10%
Pharmacology, Toxicology and Pharmaceutical Science 3 5%
Nursing and Health Professions 1 2%
Other 2 3%
Unknown 3 5%

Attention Score in Context

This research output has an Altmetric Attention Score of 3. 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 15 September 2015.
All research outputs
#4,007,830
of 13,449,710 outputs
Outputs from Clinical Epigenetics
#293
of 662 outputs
Outputs of similar age
#73,600
of 241,587 outputs
Outputs of similar age from Clinical Epigenetics
#21
of 28 outputs
Altmetric has tracked 13,449,710 research outputs across all sources so far. This one is in the 49th percentile – i.e., 49% of other outputs scored the same or lower than it.
So far Altmetric has tracked 662 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.7. This one has gotten more attention than average, scoring higher than 53% 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 241,587 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 66% of its contemporaries.
We're also able to compare this research output to 28 others from the same source and published within six weeks on either side of this one. This one is in the 21st percentile – i.e., 21% of its contemporaries scored the same or lower than it.