HINT1 inhibits beta-catenin/TCF4, USF2 and NFkappaB activity in human hepatoma cells.
HINT1 inhibits beta-catenin/TCF4, USF2 and NFkappaB activity in human hepatoma cells.
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DOI：
10.1002/ijc.24072
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发表时间：
2009-04-01
影响因子：
6.4
通讯作者：
Weinstein, I. Bernard
中科院分区：
文献类型：
--
作者：
Wang, Lin;Li, Haiyang;Zhang, Yujing;Santella, Regina M.;Weinstein, I. Bernard
在这项研究中，我们探索了一种新的肿瘤抑制基因--HINT与人类肝癌的相关性。人肝癌细胞株Hep3B和HepG2表达HINT1蛋白的水平很低，而HuH7细胞的HINT1蛋白表达水平相对较高。在Hep3B和HepG2细胞中，Hint1的启动子区域部分甲基化，经5-氮杂脱氧胞苷处理后，HINT1蛋白和Hint1mRNA在Hep3B和HepG2细胞中的表达增加。HINT1在HepG2细胞中的表达增加明显抑制其生长。抑制β-catenin/TCF4和USF2的转录活性，抑制内源性细胞周期蛋白D1和β-2的表达。HINT1还抑制了转录因子κB的活性，并抑制了内源性p65蛋白向细胞核的转位。因此，通过表观遗传沉默降低Hint1基因的表达，可能通过增加转录因子β-Catenin、Usf2和NFκB控制的基因的表达，在促进人类肝癌亚群的生长中发挥作用。
In this study we explored the relevance of Hint, a novel tumor suppressor gene, to human hepatoma. The human hepatoma cell lines Hep3B and HepG2 express very low levels of the HINT1 protein but the Huh7 cells express a relatively high level. In Hep3B and HepG2 cells, but not in Huh7 cells, the promoter region of Hint1 is partially methylated and treatment with 5-Azadcdeoxycytidine increased expression of the HINT1 protein and Hint1 mRNA in Hep3B and HepG2 cells. Increased expression of HINT1 in HepG2 cells markedly inhibited their growth. It also inhibited the transcriptional activities of β-catenin/TCF4, and USF2, and inhibited the expression of endogenous cyclin D1 and TGFβ2. Furthermore, HINT1 co-immunoprecipitated with USF2 in extracts of Hep2 cells. HINT1 also inhibited NFκB transcription factor reporter activity and inhibited translocation of the endogenous p65 protein to the nucleus of HepG2 cells. Therefore, decreased expression of the Hint1 gene through epigenetic silencing may play a role in enhancing the growth of a subset of human hepatoma by increasing the expression of genes controlled by the transcription factors β-catenin, USF2, and NFκB.
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影响因子：
5.3
作者：
Lee, YN;Razin, E
通讯作者：
Razin, E
影响因子：
4.8
作者：
Grau, AM;Datta, PK;Beauchamp, RD
通讯作者：
Beauchamp, RD
影响因子：
8
作者：
Lu, T;Sathe, SS;Stark, GR
通讯作者：
Stark, GR
影响因子：
4.8
作者：
Razin, E;Zhang, ZC;Rivera, J
通讯作者：
Rivera, J
DOI：
10.1196/annals.1386.024
发表时间：
2006-01-01
期刊：
ESTROGENS AND HUMAN DISEASES
影响因子：
--
作者：
Buck, Miriam B.;Knabbe, Cornelius
通讯作者：
Knabbe, Cornelius