Snail as a key regulator of PRL-3 gene in colorectal cancer
Snail as a key regulator of PRL-3 gene in colorectal cancer
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蜗牛是结直肠癌中 PRL-3 基因的关键调节因子
DOI：
10.4161/cbt.12.8.15981
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发表时间：
2011-10-15
影响因子：
3.6
通讯作者：
Li, Jian-Ming
中科院分区：
文献类型：
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作者：
Zheng, Ping;Meng, Hui-Min;Li, Jian-Ming
结直肠癌（CRC）中关键转移基因PRL-3的调节因子在很大程度上仍然未知。我们在PRL-3启动子区域（位于-642至-383）发现了三个潜在的结合位点，Snail是参与上皮-间质转化（EMT）的关键转录因子。此外，我们的研究结果表明，蜗牛结合位点之一（位于-624至-619）是维持人类PRL-3基因启动子活性的关键因素。在螺结合位点（-624 ~ -619）突变后，PRL-3启动子的转录活性被破坏。钉螺可调节结直肠癌细胞株启动子活性和PRL-3蛋白表达。在结直肠癌和结直肠癌转移淋巴结的临床样本中，PRL-3蛋白的表达与Snail蛋白的表达相关。通过基因过表达和敲低的方法进行的功能研究表明，蜗牛促进了人结直肠癌细胞的增殖、细胞粘附和迁移。在PRL-3稳定敲除的SW480细胞中，Snail上调后细胞增殖增加。我们的数据首先揭示了转录因子Snail是CRC中PRL-3的关键调节因子。蜗牛与PRL-3之间的联系提示了蜗牛参与结直肠癌进展和转移的一种新的潜在机制。
The regulators of a key metastasis gene PRL-3 in colorectal cancer (CRC) are still largely unknown. We found three potential binding sites of Snail, a key transcriptional factor involved in the epithelial-mesenchymal transition (EMT), in the region of PRL-3 promoter (located at -642 to -383). Moreover, our results showed that one of the Snail binding sites (located at -624 to -619) was the key element to maintain promoter activity of human PRL-3 gene. The transcriptional activity of PRL-3 promoter was abolished after the Snail binding site (located at -624 to -619) was mutated. Both promoter activity and protein expression of PRL-3 in CRC cell lines could be regulated by Snail. In clinical samples of CRC and metastatic lymph node of CRC, expression of PRL-3 protein was correlated with expression of Snail protein. Functional studies using gene over-expression and knockdown methods indicated that Snail promoted proliferation, cell adhesion and migration of human CRC cells. In SW480 cells with PRL-3 stable knockdown, cell proliferation increased after Snail was up-regulated. Our data first reveal transcriptional factor Snail as a key regulator of PRL-3 in CRC. The link between Snail and PRL-3 suggests a new potential mechanism of Snail contributing to progression and metastasis of CRC.