机构：[1]Chinese Acad Med Sci, Natl Lab Med Mol Biol, Inst Basic Med Sci, Beijing 100005, Peoples R China;[2]Peking Union Med Coll, Natl Human Genome Ctr, Beijing 100005, Peoples R China;[3]Peking Univ, Key Lab Carcinogenesis & Translat Res, Minist Educ, Dept Oncol G1,Sch Oncol,Beijing Canc Hosp & Inst, Beijing 100142, Peoples R China;[4]MOST, High Tech Res & Dev Ctr, Beijing 100862, Peoples R China;[5]Beijing Union Med Coll Hosp, Dept Internal Med, Beijing 100730, Peoples R China;[6]Beijing Tiantan Hosp, Dept Neurosurg, Beijing 100050, Peoples R China重点科室诊疗科室神经外科神经外科首都医科大学附属天坛医院
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. (C) 2008 Wiley-Liss, Inc.
基金：
National Natural Sciences Foundation of ChinaNational Natural Science Foundation of China [30825023, 30571039, 30721063, 30430200]; "973" projectsNational Basic Research Program of China [2004CB518604, 2005CB522507, 2006CB504100]; "S63" project [2006AA02Z137, 2006AA0A304]; Program for New Century Excellent Talents in UniversityProgram for New Century Excellent Talents in University (NCET) [NCET-07-0505]
第一作者机构：[1]Chinese Acad Med Sci, Natl Lab Med Mol Biol, Inst Basic Med Sci, Beijing 100005, Peoples R China;[2]Peking Union Med Coll, Natl Human Genome Ctr, Beijing 100005, Peoples R China;[3]Peking Univ, Key Lab Carcinogenesis & Translat Res, Minist Educ, Dept Oncol G1,Sch Oncol,Beijing Canc Hosp & Inst, Beijing 100142, Peoples R China;
通讯作者：
通讯机构：[1]Chinese Acad Med Sci, Natl Lab Med Mol Biol, Inst Basic Med Sci, Beijing 100005, Peoples R China;[2]Peking Union Med Coll, Natl Human Genome Ctr, Beijing 100005, Peoples R China;
推荐引用方式(GB/T 7714)：
Gao Jing,Chen Tao,Liu Jin,et al.Loss of NECL1, a Novel Tumor Suppressor, Can be Restored in Glioma by HDAC Inhibitor-Trichostatin A Through Sp1 Binding Site[J].GLIA.2009,57(9):989-999.doi:10.1002/glia.20823.
APA：
Gao, Jing,Chen, Tao,Liu, Jin,Liu, Wei,Hu, Guangyu...&Peng, Xiaozhong.(2009).Loss of NECL1, a Novel Tumor Suppressor, Can be Restored in Glioma by HDAC Inhibitor-Trichostatin A Through Sp1 Binding Site.GLIA,57,(9)
MLA：
Gao, Jing,et al."Loss of NECL1, a Novel Tumor Suppressor, Can be Restored in Glioma by HDAC Inhibitor-Trichostatin A Through Sp1 Binding Site".GLIA 57..9(2009):989-999
