EGR1 mediates miR-203a suppress the hepatocellular carcinoma cells progression by targeting HOXD3 through EGFR signaling pathway.
EGR1 mediates miR-203a suppress the hepatocellular carcinoma cells progression by targeting HOXD3 through EGFR signaling pathway.
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EGR1通过EGFR信号通路靶向HOXD3介导miR-203a抑制肝癌细胞进展
DOI：
10.18632/oncotarget.9605
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发表时间：
2016-07-19
期刊：
影响因子：
--
通讯作者：
Huang C
中科院分区：
文献类型：
--
作者：
Wang L;Sun H;Wang X;Hou N;Zhao L;Tong D;He K;Yang Y;Song T;Yang J;Huang C
Egr1在癌症进展中起着关键作用。然而，它在肝细胞癌中的确切作用尚未阐明。在本研究中，我们发现Egr1的过表达通过与miR-203a启动子序列结合来抑制肝癌细胞的增殖和增加细胞的凋亡。此外，我们还研究了miR-203a在肝癌细胞进展中的作用。我们验证了miR-203a的过表达与Egr1在调节细胞进程中的作用是一致的。通过生物信息学分析和荧光素酶活性测定，我们证实miR-203a以Hoxd3为靶点。沉默Hoxd3可以通过EGFR/AKT和ERK细胞信号通路靶向EGFR，阻断G2/M期转变，增加细胞凋亡，降低细胞周期和细胞凋亡相关蛋白EGFR、p-AKT、p-ERK、CCNB1、CDK1和Bcl2的表达。同样，Hoxd3的恢复可以抵消miR-203a表达的影响。总之，我们的发现首次证明Egr1在miR-203a的转录调控中起关键作用，miR-203a通过EGFR相关的细胞信号通路靶向Hoxd3而发挥抑癌基因的作用，从而抑制肝癌的发生。
EGR1 plays a critical role in cancer progression. However, its precise role in hepatocellular carcinoma has not been elucidated. In this study, we found that the overexpression of EGR1 suppresses hepatocellular carcinoma cell proliferation and increases cell apoptosis by binding to the miR-203a promoter sequence. In addition, we investigated the function of miR-203a on progression of HCC cells. We verified that the effect of overexpression of miR-203a is consistent with that of EGR1 in regulation of cell progression. Through bioinformatic analysis and luciferase assays, we confirmed that miR-203a targets HOXD3. Silencing HOXD3 could block transition of the G2/M phase, increase cell apoptosis, decrease the expression of cell cycle and apoptosis-related proteins, EGFR, p-AKT, p-ERK, CCNB1, CDK1 and Bcl2 by targeting EGFR through EGFR/AKT and ERK cell signaling pathways. Likewise, restoration of HOXD3 counteracted the effects of miR-203a expression. In conclusion, our findings are the first to demonstrate that EGR1 is a key player in the transcriptional control of miR-203a, and that miR-203a acts as an anti-oncogene to suppress HCC tumorigenesis by targeting HOXD3 through EGFR-related cell signaling pathways.
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影响因子：
11.2
作者：
Li Y;Kuscu C;Banach A;Zhang Q;Pulkoski-Gross A;Kim D;Liu J;Roth E;Li E;Shroyer KR;Denoya PI;Zhu X;Chen L;Cao J
通讯作者：
Cao J
影响因子：
--
作者：
Hu, Guanghui;Lai, Peng;Xu, Yunfei
通讯作者：
Xu, Yunfei
影响因子：
4
作者：
Cheng Shaoqiang;Zhang Yue;Zhang Qingyuan
通讯作者：
Zhang Qingyuan
影响因子：
4
作者：
Braconi C;Henry JC;Kogure T;Schmittgen T;Patel T
通讯作者：
Patel T
影响因子：
2.7
作者：
Manley, NR;Capecchi, MR
通讯作者：
Capecchi, MR