Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Department of Gynecology and Obstetrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Biol Chem. 2018 Jul 26;399(8):911-919. doi: 10.1515/hsz-2018-0131.
Hedgehog (Hh) signaling is involved in the progression of hepatocellular carcinoma (HCC), while its detailed mechanisms are not well illustrated. Our present study revealed that the expression of Gli1, while not Gli2 or Gli3, is significantly increased in HCC cell lines and 20/28 (71.4%) HCC tissues as compared with their corresponding controls. Over expression of Gli1 can promote the migration, invasion and epithelial-mesenchymal transition (EMT) of HCC cells. Gli1 can increase the expression of Twist, while not other EMT transcription factors such as Snail, ZEB1 or Slug. Gli1 increases the transcription of Twist while it has no significant effect on the protein or mRNA stability. Chromatin immunoprecipitation-polymerase chain reaction confirms that Gli1 can directly bind to the promoter of Twist, in which the third binding site is essential for Gli1 induced transcription. Collectively, our data suggest that upregulation of Twist is involved in Gli1 induced migration and invasion of HCC cells.
hedgehog (Hh) 信号通路参与了肝细胞癌 (HCC) 的进展，但其详细机制尚不清楚。本研究显示Gli1 的表达在 HCC 细胞系和 20/28 (71.4%) HCC 组织中明显高于相应的对照组，而 Gli2 或 Gli3 的表达没有明显变化。Gli1 的过表达可以促进 HCC 细胞的迁移、侵袭和上皮间质转化 (EMT)。Gli1 可以增加 Twist 的表达，而不是其他 EMT 转录因子，如 Snail、ZEB1 或 Slug。Gli1 增加了 Twist 的转录，而对其蛋白或 mRNA 的稳定性没有显著影响。染色质免疫沉淀聚合酶链反应证实 Gli1 可以直接结合 Twist 的启动子，其中第三个结合位点对于 Gli1 诱导的转录是必需的。总之，我们的数据表明 Twist 的上调参与了 Gli1 诱导的 HCC 细胞迁移和侵袭。
