Homeobox C8 is a transcriptional repressor of E-cadherin gene expression in non-small cell lung cancer
Homeobox C8 is a transcriptional repressor of E-cadherin gene expression in non-small cell lung cancer
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同源盒 C8 是非小细胞肺癌中 E-钙粘蛋白基因表达的转录抑制因子
DOI：
10.1016/j.biocel.2019.06.005
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发表时间：
2019
影响因子：
4
通讯作者：
Li Yong
中科院分区：
文献类型：
--
作者：
Zhang Jie;Yang Mengqi;Li Dongjia;Zhu Siqi;Zou Jin;Xu Shanshan;Wang Yun;Shi Jialu;Li Yong
E-钙粘附素表达缺失是肿瘤进展过程中上皮-间充质转化(EMT)的标志。由于先前的发现表明同源盒C8(HOXC8)促进非小细胞肺癌(NSCLC)的EMT，我们调查了E-钙粘蛋白是否是HOXC8蛋白的靶标。在本研究中，我们报道HOXC8与E-钙粘蛋白启动子结合，并作为转录抑制因子在非小细胞肺癌中调节E-钙粘蛋白的转录。我们进一步表明，E-钙粘蛋白的缺失导致NSCLC细胞锚定非依赖性生长和迁移增加，而HOXC8基因敲除所介导的抑制作用可以通过减少E-钙粘蛋白的表达而在很大程度上被挽救，提示HOXC8-E-钙粘蛋白途径参与了肺癌的进展。此外，对E-cadherin和HOXC8表达的分析表明，HOXC8的表达与E-cadherin的表达缺失密切相关，而高HOXC8/低E-cadherin的表达与肺癌患者的预后显著相关。综上所述，这些数据表明E-钙粘蛋白是HOXC8的靶基因，E-钙粘蛋白的缺失促进了非小细胞肺癌的生长和迁移。
Loss of E-cadherin expression is a hallmark of epithelial-mesenchymal transition (EMT) in tumor progression. Because previous findings suggested that homeobox C8 (HOXC8) promotes EMT in non-small-cell lung cancer (NSCLC), we investigated whether E-cadherin is a target of HOXC8 protein. In this study, we report that HOXC8 binds to the E-cadherin promoter and acts as a transcriptional repressor to regulate E-cadherin transcription in NSCLC. We further show that loss of E-cadherin leads to an increase in anchorage-independent growth and migration of NSCLC cells, and the inhibitory effects mediated by HOXC8 knockdown can be largely rescued by reduction of E-cadherin expression, suggesting that the HOXC8-E-cadherin pathway is involved in lung cancer progression. Moreover, analysis of E-cadherin and HOXC8 expression indicates that expression of HOXC8 is strongly correlated with loss of E-cadherin expression, and high HOXC8 / low E-cadherin expression is significantly correlated with poor survival for lung cancer patients. Taken together, these data indicate that E-cadherin is a target gene of HOXC8 and that the loss of E-cadherin promotes the growth and migration of NSCLC.