Sp1-Induced SETDB1 Overexpression Transcriptionally Inhibits HPGD in a β-Catenin-Dependent Manner and Promotes the Proliferation and Metastasis of Gastric Cancer.
Sp1-Induced SETDB1 Overexpression Transcriptionally Inhibits HPGD in a β-Catenin-Dependent Manner and Promotes the Proliferation and Metastasis of Gastric Cancer.
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SP1诱导的SETDB1过表达在转录上以β-catenin依赖性方式抑制HPGD，并促进胃癌的增殖和转移。
DOI：
10.5230/jgc.2022.22.e26
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发表时间：
2022-10
影响因子：
2.5
通讯作者：
Li L
中科院分区：
文献类型：
--
作者：
Fan Y;Yang L;Ren Y;Wu Y;Li L;Li L
胃癌（GC）发病率和死亡率较高，手术治疗和药物化疗的治愈率并不理想。因此，开发新的治疗策略是必要的。我们的目的是确定 Sp1 调节 GC 进展的潜在机制。通过定量逆转录聚合酶链反应和蛋白质印迹分析检测 Sp1、β-连环蛋白、SET 结构域分叉 1 (SETDB1) 和 15-羟基前列腺素脱氢酶 (HPGD) 的水平。通过AnimalTFDB预测SETDB1的靶点，并使用双荧光素酶报告基因检测来确认Sp1、β-catenin和SETDB1的结合。通过尾静脉注射HGC27或AGS细胞（1×106细胞/小鼠）建立GC模型。采用免疫组化法检测Ki67水平，并进行苏木精和伊红染色评价GC小鼠肿瘤转移情况。 HPGD 受到抑制，而 GC 组织和细胞系中 Sp1、β-catenin 和 SETDB1 的蛋白水平上调。 HPGD过表达或SETDB1沉默抑制GC细胞的增殖、侵袭和迁移，而Sp1以β-catenin依赖性方式调节GC细胞的增殖、侵袭和迁移。此外，HPGD作为SETDB1的靶点，受到SETDB1的负调控；此外，Sp1 和 β-catenin 与 SETDB1 启动子结合并负向调节 HPGD 表达。我们证明 Sp1 通过 SETDB1/HPGD 轴调节 GC 进展。我们的研究结果表明，Sp1 通过 SETDB1 以 β-catenin 依赖性方式转录抑制 HPGD，并促进 GC 细胞的增殖和转移。
Gastric cancer (GC) has high morbidity and mortality, the cure rate of surgical treatment and drug chemotherapy is not ideal. Therefore, development of new treatment strategies is necessary. We aimed to identify the mechanism underlying Sp1 regulation of GC progression. The levels of Sp1, β-catenin, SET domain bifurcated 1 (SETDB1), and 15-hydroxyprostaglandin dehydrogenase (HPGD) were detected by quantitative reverse transcription polymerase chain reaction and western blot analysis. The targets of SETDB1 were predicted by AnimalTFDB, and dual-luciferase reporter assay was used for confirming the combination of Sp1, β-catenin, and SETDB1. HGC27 or AGS cells (1×106 cells/mouse) were injected into mice via the caudal vein for GC model establishment. The level of Ki67 was detected using immunohistochemistry, and hematoxylin and eosin staining was performed for evaluating tumor metastasis in mice with GC. HPGD was inhibited, while the protein levels of Sp1, β-catenin, and SETDB1 were up-regulated in GC tissues and cell lines. HPGD overexpression or SETDB1 silencing inhibited the proliferation, invasion, and migration of GC cells, and Sp1 regulated the proliferation, invasion, and migration of GC cells in a β-catenin-dependent manner. Furthermore, HPGD served as a target of SETDB1, and it was negatively regulated by SETDB1; additionally, Sp1 and β-catenin bound to the SETDB1 promoter and negatively regulated HPGD expression. We proved that Sp1 regulated GC progression via the SETDB1/HPGD axis. Our findings revealed that Sp1 transcriptionally inhibited HPGD via SETDB1 in a β-catenin-dependent manner and promoted the proliferation and metastasis of GC cells.
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影响因子：
13
作者：
Huang, Chen;Xie, Keping
通讯作者：
Xie, Keping
DOI：
10.1006/bbrc.1997.6831
发表时间：
1997-06-27
影响因子：
3.1
作者：
Matsuo, M;Ensor, CM;Tai, HH
通讯作者：
Tai, HH
影响因子：
5.3
作者：
Mir, Rafeeq;Sharma, Ankita;Galande, Sanjeev
通讯作者：
Galande, Sanjeev
SETDB1通过表观遗传学沉默p21表达促进结直肠癌的进展
影响因子：
9
作者：
Cao, Nan;Yu, Yali;Ye, Mei
通讯作者：
Ye, Mei
SETDB1通过上调CCND1和MMP9表达促进胃癌发生和转移
影响因子：
7.3
作者：
Shang, Wenjing;Wang, Yue;Jia, Jihui
通讯作者：
Jia, Jihui