SND1 acts upstream of SLUG to regulate the epithelial-mesenchymal transition (EMT) in SKOV3 cells
SND1 acts upstream of SLUG to regulate the epithelial-mesenchymal transition (EMT) in SKOV3 cells
复制标题
SND1 作用于 SLUG 上游，调节 SKOV3 细胞中的上皮间质转化 (EMT)
DOI：
10.1096/fj.201801728r
复制
发表时间：
2019-03-01
期刊：
影响因子：
4.8
通讯作者：
Yang, Jie
中科院分区：
文献类型：
--
作者：
Xin, Lingbiao;Zhao, Ran;Yang, Jie
葡萄球菌含核酸酶结构域蛋白1（SND 1）已被报道为多种癌症中的癌蛋白，涉及多个过程，包括增殖，血管生成和转移。然而，转移的潜在机制在很大程度上仍然未知。在此，通过使用具有高转移能力的卵巢癌细胞系SKOV 3，我们发现SND 1的功能丧失显著抑制了SKOV 3细胞的侵袭和迁移。然后，我们进行了基因表达谱，并进一步验证（通过使用定量PCR和Western印迹分析），SND 1的功能丧失导致上皮标志物，如上皮钙粘蛋白和claudin 1的上调，以及间充质标志物，包括神经钙粘蛋白和波形蛋白的下调。此外，我们阐明了SLUG，一种参与上皮-间充质转化和转移的关键转录因子，通过调节N-CAD和Vim表达（或E-CAD和CLDN 1）作为SND 1促进的上皮-间充质转化过程的重要效应子。潜在的分子机制表明，SND 1调节基因转录激活SLUG通过增加染色质的可及性，通过招募的乙酰转移酶GCN 5和CBP/p300的SLUG启动子近端区域。总之，SND 1被鉴定为SLUG的新型上游调节因子，其在调节E-CAD/N-CAD表达转换中起重要作用。赵，R.，雷，J.，宋杰Yu，L.，（1991 - 1995），美国，加奥河，巴西-地哈C Ren，Y.，刘，X.，Liu，Y.，姚，Z.，Yang，J. SND 1在SLUG上游起作用以调节SKOV 3细胞中的上皮-间充质转化（EMT）。
Staphylococcal nuclease domain-containing protein 1 (SND1) has been reported as an oncoprotein in a variety of cancers involving multiple processes, including proliferation, angiogenesis, and metastasis. However, the mechanisms underlying metastasis remain largely unknown. Herein, by using the ovarian cancer cell line SKOV3, which has high metastasis ability, we showed that loss-of-function of SND1 dramatically suppressed the invasion and migration of SKOV3 cells. We then performed gene expression profiles and further verified (by use of quantitative PCR and Western blot analysis) that loss-of-function of SND1 resulted in up-regulation of epithelial markers, such as epithelial cadherin and claudin 1, and down-regulation of mesenchymal markers, including neural cadherin and vimentin. Moreover, we illustrated that SLUG, a key transcription factor implicated in epithelial-mesenchymal transition and metastasis, acts as an essential effector of the SND1-promoted epithelial-mesenchymal transition process via regulating N-CAD and VIM expression (or E-CAD and CLDN1). The underlying molecular mechanisms illustrated that SND1 regulates the gene transcriptional activation of SLUG by increasing chromatin accessibility through the recruitment of the acetyltransferases GCN5 and CBP/p300 to the SLUG promoter proximal region. Overall, SND1 was identified as a novel upstream regulator of SLUG, which plays important roles in regulating the E-CAD/N-CAD expression switch.Xin, L., Zhao, R., Lei, J., Song, J., Yu, L., Gao, R., Ha, C., Ren, Y., Liu, X., Liu, Y., Yao, Z., Yang, J. SND1 acts upstream of SLUG to regulate the epithelial-mesenchymal transition (EMT) in SKOV3 cells.