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Transcriptional Suppression, DNA Methylation, and Histone Deacetylation of the Regulator of G-Protein Signaling 10 (RGS10) Gene in Ovarian Cancer Cells

Overview of attention for article published in PLOS ONE, March 2013
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Title
Transcriptional Suppression, DNA Methylation, and Histone Deacetylation of the Regulator of G-Protein Signaling 10 (RGS10) Gene in Ovarian Cancer Cells
Published in
PLOS ONE, March 2013
DOI 10.1371/journal.pone.0060185
Pubmed ID
Authors

Mourad W. Ali, Ercan Cacan, Yuying Liu, Jennifer Young Pierce, William T. Creasman, Mandi M. Murph, Rajgopal Govindarajan, Scott T. Eblen, Susanna F. Greer, Shelley B. Hooks

Abstract

RGS10 regulates ovarian cancer cell growth and survival, and RGS10 expression is suppressed in cell models of ovarian cancer chemoresistance. However, the mechanisms governing RGS10 expression in ovarian cancer are poorly understood. Here we report RGS10 suppression in primary ovarian cancer and CAOV-3 ovarian cancer cells compared to immortalized ovarian surface epithelial (IOSE) cells, and in A2780-AD chemoresistant cells compared to parental A2780 cells. RGS10-1 and RGS10-2 transcripts are expressed in ovarian cancer cells, but only RGS10-1 is suppressed in A2780-AD and CAOV-3 cells, and the RGS10-1 promoter is uniquely enriched in CpG dinucleotides. Pharmacological inhibition of DNA methyl-transferases (DNMTs) increased RGS10 expression, suggesting potential regulation by DNA methylation. Bisulfite sequencing analysis identified a region of the RGS10-1 promoter with significantly enhanced DNA methylation in chemoresistant A2780-AD cells relative to parental A2780 cells. DNA methylation in CAOV-3 and IOSE cells was similar to A2780 cells. More marked differences were observed in histone acetylation of the RGS10-1 promoter. Acetylated histone H3 associated with the RGS10-1 promoter was significantly lower in A2780-AD cells compared to parental cells, with a corresponding increase in histone deacetylase (HDAC) enzyme association. Similarly, acetylated histone levels at the RGS10-1 promoter were markedly lower in CAOV-3 cells compared to IOSE cells, and HDAC1 binding was doubled in CAOV-3 cells. Finally, we show that pharmacological inhibition of DNMT or HDAC enzymes in chemoresistant A2780-AD cells increases RGS10 expression and enhances cisplatin toxicity. These data suggest that histone de-acetylation and DNA methylation correlate with RGS10 suppression and chemoresistance in ovarian cancer. Markers for loss of RGS10 expression may identify cancer cells with unique response to therapeutics.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 28 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Iran, Islamic Republic of 1 4%
Netherlands 1 4%
Unknown 26 93%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 7 25%
Student > Master 5 18%
Researcher 4 14%
Student > Bachelor 2 7%
Student > Doctoral Student 1 4%
Other 3 11%
Unknown 6 21%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 8 29%
Medicine and Dentistry 6 21%
Agricultural and Biological Sciences 5 18%
Social Sciences 1 4%
Neuroscience 1 4%
Other 0 0%
Unknown 7 25%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 23 March 2013.
All research outputs
#20,185,720
of 22,701,287 outputs
Outputs from PLOS ONE
#172,966
of 193,818 outputs
Outputs of similar age
#172,684
of 197,452 outputs
Outputs of similar age from PLOS ONE
#4,450
of 5,434 outputs
Altmetric has tracked 22,701,287 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 193,818 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.0. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 5,434 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.