Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2009-5-14
pubmed:abstractText
Nectin-like molecule 1 (NECL1)/CADM3/IGSF4B/TSLL1/SynCAM3 is a neural tissue-specific immunoglobulin-like cell-cell adhesion molecule downregulated at the mRNA level in 12 human glioma cell lines. Here we found that the expression of NECL1 was lost in six glioma cell lines and 15 primary glioma tissues at both RNA and protein levels. Re-expression of NECL1 into glioma cell line U251 would repress cell proliferation in vitro by inducing cell cycle arrest. And also NECL1 could decrease the growth rate of tumors in nude mice in vivo. To further investigate the mechanism why NECL1 was silenced in glioma, the basic promoter region located at -271 to +81 in NECL1 genomic sequence was determined. DNA bisulfite sequencing was performed to study the methylation status of CpG islands in NECL1 promoter; however, no hypermethylated CpG site was found. Additionally, the activity of histone deacetylase (HDACs) in glioma was higher than that in normal brain tissues, and the expression of NECL1 in glioma cell lines could be reactivated by HDACs inhibitor-Trichostatin A (TSA). So the loss of NECL1 in glioma was at least partly caused by histone deacetylation. Luciferase reporter assays, chromatin immunoprecipitation and co-immunoprecipitation (co-IP) assays indicated that Sp1 played an important role in this process by binding to either HDAC1 in untreated glioma cells or p300/CBP in TSA treated cells. Our finding suggests that NECL1 may act as a tumor suppressor in glioma and loss of it in glioma may be caused by histone deacetylation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/CADM3 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Cell Adhesion Molecules, http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylase Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylases, http://linkedlifedata.com/resource/pubmed/chemical/Hydroxamic Acids, http://linkedlifedata.com/resource/pubmed/chemical/Igsf4b protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulins, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Sp1 Transcription Factor, http://linkedlifedata.com/resource/pubmed/chemical/p300-CBP Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/trichostatin A
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1098-1136
pubmed:author
pubmed:copyrightInfo
(c) 2008 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:volume
57
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
989-99
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:19062177-Acetylation, pubmed-meshheading:19062177-Animals, pubmed-meshheading:19062177-Binding Sites, pubmed-meshheading:19062177-Brain, pubmed-meshheading:19062177-Brain Neoplasms, pubmed-meshheading:19062177-Cell Adhesion Molecules, pubmed-meshheading:19062177-Cell Line, Tumor, pubmed-meshheading:19062177-Cell Proliferation, pubmed-meshheading:19062177-CpG Islands, pubmed-meshheading:19062177-DNA Methylation, pubmed-meshheading:19062177-Female, pubmed-meshheading:19062177-Glioma, pubmed-meshheading:19062177-Histone Deacetylase Inhibitors, pubmed-meshheading:19062177-Histone Deacetylases, pubmed-meshheading:19062177-Humans, pubmed-meshheading:19062177-Hydroxamic Acids, pubmed-meshheading:19062177-Immunoglobulins, pubmed-meshheading:19062177-Membrane Proteins, pubmed-meshheading:19062177-Methylation, pubmed-meshheading:19062177-Mice, pubmed-meshheading:19062177-Mice, Nude, pubmed-meshheading:19062177-Neoplasm Transplantation, pubmed-meshheading:19062177-Promoter Regions, Genetic, pubmed-meshheading:19062177-RNA, Messenger, pubmed-meshheading:19062177-Sequence Analysis, DNA, pubmed-meshheading:19062177-Sp1 Transcription Factor, pubmed-meshheading:19062177-p300-CBP Transcription Factors
pubmed:year
2009
pubmed:articleTitle
Loss of NECL1, a novel tumor suppressor, can be restored in glioma by HDAC inhibitor-Trichostatin A through Sp1 binding site.
pubmed:affiliation
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, National Human Genome Center, Beijing 100005, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't