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Nemo-like kinase as a negative regulator of nuclear receptor Nurr1 gene transcription in prostate cancer

Overview of attention for article published in BMC Cancer, March 2016
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Title
Nemo-like kinase as a negative regulator of nuclear receptor Nurr1 gene transcription in prostate cancer
Published in
BMC Cancer, March 2016
DOI 10.1186/s12885-016-2291-4
Pubmed ID
Authors

Jian Wang, Zhi-Hong Yang, Hua Chen, Hua-Hui Li, Li-Yong Chen, Zhu, Ying Zou, Cong-Cong Ding, Jing Yang, Zhi-Wei He

Abstract

Nurr1, a member of the orphan receptor family, plays an important role in several types of cancer. Our previous work demonstrated that increased expression of Nurr1 plays a significant role in the initiation and progression of prostate cancer (PCa), though the mechanisms for regulation of Nurr1 expression remain unknown. In this study, we investigated the hypothesis that Nemo-like kinase (NLK) is a key regulator of Nurr1 expression in PCa. Immunohistochemistry and Western blot analysis were used to evaluate levels of NLK and Nurr1 in prostatic tissues and cell lines. The effects of overexpression or knockdown of Nurr1 were evaluated in PCa cells through use of PCR, Western blots and promoter reporter assays. The role of Nurr1 promoter cis element was studied by creation of two mutant Nurr1 promoter luciferase constructs, one with a mutated NF-κB binding site and one with a mutated CREB binding site. In addition, three specific inhibitors were used to investigate the roles of these proteins in transcriptional activation of Nurr1, including BAY 11-7082 (NF-κB inhibitor), KG-501 (CREB inhibitor) and ICG-001 (CREB binding protein, CBP, inhibitor). The function of CBP in NLK-mediated regulation of Nurr1 expression was investigated using immunofluorescence, co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation assays (ChIPs). NLK expression was inversely correlated with Nurr1 expression in prostate cancer tissues and cell lines. Overexpression of NLK suppressed Nurr1 promoter activity, leading to downregulation of Nurr1 expression. In contrast, knockdown of NLK demonstrated opposite results, leading to upregulation of Nurr1. When compared with the wild-type Nurr1 promoter, mutation of NF-κB- and CREB-binding sites of the Nurr1 promoter region significantly reduced the upregulation of Nurr1 induced by knockdown of NLK in LNCaP cells; treatment with inhibitors of CREB, CBP and NF-κB led to similar results. We also found that NLK directly interacts with CBP, that knockdown of NLK significantly increases the recruitment of CBP to both NF-κB- and CREB-binding sites, and that regulation of NLK on Nurr1 expression is abrogated by knockdown of CBP. Our results suggest that NLK inhibits transcriptional activation of Nurr1 gene by impeding CBP's role as a co-activator of NF-κB and CREB in prostate cancer.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 16 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 16 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 4 25%
Student > Ph. D. Student 4 25%
Researcher 3 19%
Student > Doctoral Student 1 6%
Student > Bachelor 1 6%
Other 1 6%
Unknown 2 13%
Readers by discipline Count As %
Agricultural and Biological Sciences 5 31%
Biochemistry, Genetics and Molecular Biology 3 19%
Chemistry 2 13%
Business, Management and Accounting 1 6%
Immunology and Microbiology 1 6%
Other 1 6%
Unknown 3 19%
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 03 April 2016.
All research outputs
#20,317,110
of 22,858,915 outputs
Outputs from BMC Cancer
#6,503
of 8,319 outputs
Outputs of similar age
#255,093
of 301,001 outputs
Outputs of similar age from BMC Cancer
#122
of 154 outputs
Altmetric has tracked 22,858,915 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 8,319 research outputs from this source. They receive a mean Attention Score of 4.3. 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 154 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.