Loss of NECL1, a novel tumor suppressor, can be restored in glioma by HDAC inhibitor-Trichostatin A through Sp1 binding site.

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.

Gao J ，Chen T ，Liu J ，Liu W ，Hu G ，Guo X ，Yin B ，Gong Y ，Zhao J ，Qiang B ，Yuan J ，Peng X ... -  《-》

Promoter methylation and silencing of the tissue factor pathway inhibitor-2 (TFPI-2), a gene encoding an inhibitor of matrix metalloproteinases in human glioma cells.

Konduri SD ，Srivenugopal KS ，Yanamandra N ，Dinh DH ，Olivero WC ，Gujrati M ，Foster DC ，Kisiel W ，Ali-Osman F ，Kondraganti S ，Lakka SS ，Rao JS ... -  《ONCOGENE》

Epigenetic modulation of tumor suppressor CCAAT/enhancer binding protein alpha activity in lung cancer.

Tada Y ，Brena RM ，Hackanson B ，Morrison C ，Otterson GA ，Plass C ... -  《-》

E2F-HDAC complexes negatively regulate the tumor suppressor gene ARHI in breast cancer.

Lu Z ，Luo RZ ，Peng H ，Huang M ，Nishmoto A ，Hunt KK ，Helin K ，Liao WS ，Yu Y ... -  《ONCOGENE》

Requirement of a specific Sp1 site for histone deacetylase-mediated repression of transforming growth factor beta Type II receptor expression in human pancreatic cancer cells.

Zhao S ，Venkatasubbarao K ，Li S ，Freeman JW ... -  《CANCER RESEARCH》