Rpb3 promotes hepatocellular carcinoma through its N-terminus.
Rpb3 promotes hepatocellular carcinoma through its N-terminus.
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Rpb3 通过其 N 末端促进肝细胞癌发生。
DOI：
10.18632/oncotarget.2389
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发表时间：
2014-10-15
期刊：
影响因子：
--
通讯作者：
Han HX
中科院分区：
文献类型：
--
作者：
Fang ZP;Jiang BG;Zhang FB;Wang AD;Ji YM;Xu YF;Li JC;Zhou WP;Zhou WJ;Han HX
RNA聚合酶II亚单位3(Rpb3)在肝细胞癌中的表达经常上调。Rpb3表达的增加与肝细胞癌分期的提前和患者较短的无病生存期之间也有显著的关联。Rpb3过表达促进了裸鼠肝癌细胞的增殖、迁移率和肿瘤生长，而用shRNA抑制Rpb3则抑制了这些作用。在机制研究方面，我们发现Rpb3直接与Snail结合，下调E-钙粘附素，诱导肝癌细胞上皮-间充质转化(EMT)。特别是，Rpb3的N末端阻断了Rpb3与蜗牛的结合，抑制了Rpb3高表达的肝癌细胞在裸鼠体内的增殖、迁移和肿瘤生长，也抑制了DEN诱导的肝肿瘤形成。此外，Rpb3的N末端并不抑制正常肝细胞或Rpb3低表达的肝癌细胞的增殖。这些发现表明，Rpb3的N末端选择性地抑制Rpb3高表达的肝癌细胞的增殖。Rpb3的N末端可能用于治疗Rpb3高表达的肝细胞癌患者。
The expression of RNA polymerase II subunit 3 (Rpb3) was found frequent up-regulation in Hepatocellular carcinoma (HCC) tumors. Significant associations could also be drawn between increased expressions of Rpb3 and advance HCC staging and shorter disease-free survival of patients. Overexpression of Rpb3 increased HCC cell proliferation, migratory rate and tumor growth in nude mice, whereas suppression of Rpb3 using shRNA inhibited these effects. For mechanism study, we found that Rpb3 bound directly to Snail, downregulated E-cadherin, induced HCC cells epithelial-mesenchymal transition (EMT). In particular, N-terminus of Rpb3 blocked Rpb3 binding to Snail, inhibited Rpb3-high-expression HCC cells proliferation, migration, tumor growth in nude mice, and also inhibited DEN-induced liver tumorigenesis. Furthermore, N-terminus of Rpb3 did not inhibit normal liver cells or Rpb3-low-expression HCC cells proliferation. These findings suggest that N-terminus of Rpb3 selectively inhibits Rpb3-high-expression HCC cells proliferation. N-terminus of Rpb3 may be useful in treating patients diagnosed with Rpb3-high-expression HCC.
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