Transcriptional factor specificity protein 1 (SP1) promotes the proliferation of glioma cells by up-regulating midkine (MDK).
Transcriptional factor specificity protein 1 (SP1) promotes the proliferation of glioma cells by up-regulating midkine (MDK).
复制标题
转录因子特异性蛋白 1 (SP1) 通过上调中期因子 (MDK) 促进神经胶质瘤细胞的增殖。
DOI：
10.1091/mbc.e14-10-1443
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发表时间：
2015-02-01
影响因子：
3.3
通讯作者：
Zhang N
中科院分区：
文献类型：
--
作者：
Luo J;Wang X;Xia Z;Yang L;Ding Z;Chen S;Lai B;Zhang N
Midkine （MDK）的表达与包括胶质瘤在内的许多癌症的增殖有关。SP1直接上调MDK的表达，SP1-MDK轴参与胶质瘤的发生。Midkine （MDK）的表达与包括胶质瘤在内的许多癌症的增殖有关。然而，导致MDK积累的上游信号仍然难以捉摸。本研究探讨了MDK在人胶质瘤中过度表达的分子机制。分析分子脑瘤数据库以确定潜在的MDK调节因子。比较胶质瘤标本中MDK和特异性蛋白1 （SP1）的表达。染色质免疫沉淀法证实了转录调控。我们使用mdk力表达、sp1沉默的胶质瘤细胞来测试体外和体内的拯救作用。MDK和SP1在胶质瘤中的表达明显高于邻近组织，在胶质瘤临床样本和细胞系中呈正相关。人类MDK基因的启动子有一个假定的SP1结合位点。SP1与MDK基因启动子结合，直接调控MDK的表达。MDK或SP1基因沉默可抑制胶质瘤细胞的增殖，减小裸鼠肿瘤体积。在SP1沉默细胞中过表达MDK可以部分恢复SP1在体内和体外的抑制作用。SP1直接上调MDK的表达，SP1-MDK轴参与胶质瘤的发生。
Midkine (MDK) expression is associated with the proliferation of many cancers, including glioma. SP1 directly up-regulates the expression of MDK, and the SP1-MDK axis cooperates in glioma tumorigenesis. Midkine (MDK) expression is associated with the proliferation of many cancers, including glioma. However, the upstream signaling that leads to MDK accumulation remains elusive. This study investigates the molecular mechanism that induces MDK overexpression in human glioma. The Repository for Molecular Brain Neoplasia Data was analyzed to identify potential MDK regulators. Expression of MDK and specificity protein 1 (SP1) was compared in glioma specimens. Chromatin immunoprecipitation assay was used to confirm the transcriptional regulation. MDK-force–expressed, SP1-silenced glioma cells were used to test rescue effects in vitro and in vivo. MDK and SP1 expression in gliomas was significantly higher than in adjacent tissues and was positively correlated in glioma clinical samples and cell lines. The promoter of the human MDK gene has a putative SP1 binding site. SP1 binds to the promoter of the MDK gene and directly regulates MDK expression. MDK or SP1 gene silencing inhibited the proliferation of glioma cells and reduced the tumor volume in nude mice. Overexpression of MDK in SP1-silenced cells could partially rescue the SP1 inhibition effects in vivo and in vitro. SP1 directly up-regulated the expression of MDK, and the SP1-MDK axis cooperated in glioma tumorigenesis.