ArticleOncogene2005
Dinucleotide repeats negatively modulate the promoter activity of Cyr61 and is unstable in hepatocellular carcinoma patients.
Article in Oncogene, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 34 citations in OpenAlex.
- ATF3 inhibits the tumorigenesis and progression of hepatocellular carcinoma cells via upregulation of CYR61 expression.Journal of experimental & clinical cancer research : CR · 2018Article
- Emerging roles of macrosatellite repeats in genome organization and disease development.Epigenetics · 2017Review
- CCN: core regulatory proteins in the microenvironment that affect the metastasis of hepatocellular carcinoma?Oncotarget · 2016Review
- Dissection of thousands of cell type-specific enhancers identifies dinucleotide repeat motifs as general enhancer features.Genome research · 2014Article
- Microsatellite tandem repeats are abundant in human promoters and are associated with regulatory elements.PloS one · 2013Article
- CCN1 promotes tumorigenicity through Rac1/Akt/NF-κB signaling pathway in pancreatic cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2012Article
- Cyr61/CCN1 is regulated by Wnt/β-catenin signaling and plays an important role in the progression of hepatocellular carcinoma.PloS one · 2012Article
- CCN1, a candidate target for zoledronic acid treatment in breast cancer.Molecular cancer therapeutics · 2011Article
- The matricellular protein CCN1 induces fibroblast senescence and restricts fibrosis in cutaneous wound healing.Nature cell biology · 2010Article
- LIMD1 is more frequently altered than RB1 in head and neck squamous cell carcinoma: clinical and prognostic implications.Molecular cancer · 2010Article
- A GA microsatellite in the Fli1 promoter modulates gene expression and is associated with systemic lupus erythematosus patients without nephritis.Arthritis research & therapy · 2010Article
- Ets factors and a newly identified polymorphism regulate Fli1 promoter activity in lymphocytes.Molecular immunology · 2008Article
- Nucleotide sequence analyses of the MRP1 gene in four populations suggest negative selection on its coding region.BMC genomics · 2006Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cyr61 is a secreted, cysteine-rich, heparin-binding protein that mediates diverse functions including extracellular matrix formation, differentiation, cell proliferation, adhesion, migration, survival, as well as angiogenesis and tumorigenesis. In this study, we found that Cyr61 gene expression is significantly downregulated in the tumors of hepatocellular carcinoma (HCC) patients. To elucidate its mechanism of gene regulation, we examined the promoter of Cyr61 which contains two long stretches of repeats, each comprising d(CA) dinucleotide repeats downstream of HNF3beta- and ATF-binding sites. We hypothesized that the d(CA) repeats may play an important role in regulating Cyr61 promoter activity and performed promoter reporter assays to examine this. We found that a greater number of d(CA) repeats resulted in significantly lower promoter activity of the Cyr61 gene in the KB3-1 and HepG2 cell lines, but not in the MCF-7 cell line. In addition, the d(CA) repeats, but not other random sequences, were found to be important for Cyr61 promoter activity. We further demonstrate that the ATF- and HNF3beta-binding sites upstream the d(CA) repeats positively and negatively modulate Cyr61 promoter activity, respectively. An examination of the d(CA) dinucleotide patterns in the Cyr61 promoter in HCC patients revealed that approximately 32% of these patients exhibited either loss of heterozygosity or somatic mosaicism in either the tumors, adjacent normal liver tissues or both.
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