↓ Skip to main content

Promoter methylation inhibits expression of tumor suppressor KIBRA in human clear cell renal cell carcinoma

Overview of attention for article published in Clinical Epigenetics, October 2017
Altmetric Badge

About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (77th percentile)
  • High Attention Score compared to outputs of the same age and source (89th percentile)

Mentioned by

blogs
1 blog
twitter
2 X users

Citations

dimensions_citation
17 Dimensions

Readers on

mendeley
27 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
Promoter methylation inhibits expression of tumor suppressor KIBRA in human clear cell renal cell carcinoma
Published in
Clinical Epigenetics, October 2017
DOI 10.1186/s13148-017-0415-6
Pubmed ID
Authors

Katrin Schelleckes, Boris Schmitz, Giuliano Ciarimboli, Malte Lenders, Hermann J. Pavenstädt, Edwin Herrmann, Stefan-Martin Brand, Eva Brand

Abstract

KIBRA has been suggested as a key regulator of the Hippo signaling pathway, regulating organ size, cell contact inhibition, tissue regeneration as well as tumorigenesis and cystogenesis. We recently reported that human KIBRA expression depends on a complex alternative CpG-rich promoter system. Our current study aimed at the identification of epigenetic mechanisms associated with alterations in KIBRA expression regulation. We identified two separated methylation-sensitive CpG islands located to independent KIBRA promoter regions. In vitro promoter methylation analysis using human neuroblastoma (SH-SY5Y) and immortalized kidney cells (IHKE) revealed that total promoter methylation by CpG methyltransferase SssI resulted in complete abrogation of transcriptional activity (p < 0.001), while partial methylation by HpaII selectively repressed KIBRA core promoter activity in kidney cells (p < 0.001). Cell culture-based experiments demonstrated that 5-azacitidine may be used to restore KIBRA mRNA and protein levels, while overexpression of transcription factor SP1 also induced KIBRA upregulation (all p < 0.001). Furthermore, SP1 transactivation of KIBRA transcription was largely prevented by methylation of KIBRA regulatory elements (p < 0.001). Analysis of human kidney biopsies revealed that KIBRA promoter methylation was associated with human clear cell renal cell carcinoma (ccRCC; n = 8 vs 16 controls, OR = 1.921, [CI 95% = 1.369-2.695]). The subsequent determination of KIBRA mRNA levels by real-time PCR in a larger patient sample confirmed significantly reduced KIBRA expression in ccRCC (n = 32) compared to non-neoplastic human kidney tissue samples (controls, n = 32, p < 0.001). We conclude that epigenetic downregulation of tumor suppressor KIBRA may involve impaired SP1 binding to functional methylation-sensitive KIBRA promoter elements as observed in human kidney clear cell carcinoma. Our findings provide a pathophysiological basis for future studies on altered KIBRA regulation in clinical disease entities such as renal cancer.

X Demographics

X Demographics

The data shown below were collected from the profiles of 2 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 27 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 27 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 8 30%
Student > Ph. D. Student 3 11%
Student > Master 3 11%
Student > Bachelor 2 7%
Other 2 7%
Other 3 11%
Unknown 6 22%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 9 33%
Medicine and Dentistry 6 22%
Agricultural and Biological Sciences 3 11%
Chemical Engineering 1 4%
Psychology 1 4%
Other 1 4%
Unknown 6 22%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 8. 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 14 March 2019.
All research outputs
#4,026,777
of 23,005,189 outputs
Outputs from Clinical Epigenetics
#265
of 1,262 outputs
Outputs of similar age
#72,669
of 323,390 outputs
Outputs of similar age from Clinical Epigenetics
#3
of 28 outputs
Altmetric has tracked 23,005,189 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 1,262 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.5. 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 323,390 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 77% 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 has done well, scoring higher than 89% of its contemporaries.