Ophiopogonin-B Suppresses Epithelial-mesenchymal Transition in Human Lung Adenocarcinoma Cells via the Linc00668/miR-432-5p/EMT Axis
Ophiopogonin-B Suppresses Epithelial-mesenchymal Transition in Human Lung Adenocarcinoma Cells via the Linc00668/miR-432-5p/EMT Axis
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DOI：
10.7150/jca.31338
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发表时间：
2019-01-01
影响因子：
3.9
通讯作者：
Zhang, Xu
中科院分区：
文献类型：
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作者：
Hu, Cheng;Jiang, Rilei;Zhang, Xu
OP-B在体内外均能抑制腺癌A549细胞的转移和血管生成。越来越多的证据表明炎症微环境促进肿瘤转移。非小细胞肺癌（NSCLC）细胞系的数字基因表达（DGE）分析显示，OP-B下调linc 00668的表达，这促进了癌症的进展。在此，我们通过将A549细胞与LPS处理的THP-1细胞共培养来模拟炎症微环境，发现在模拟组中linc 00668的水平显著增加，而OP-B处理抑制linc 00668的水平并逆转linc 00668诱导的上皮-间质转化（EMT）。此外，linc 00668在A549细胞中过表达抑制E-cadherin的表达并诱导N-cadherin的表达，而OP-B处理逆转了这些变化。生物信息学预测和双荧光素酶报告基因检测验证了linc 00668海绵miR-432- 5 p最终作用于EMT，在炎症微环境下执行A549细胞的抗迁移功能。总之，OP-B通过linc 00668/miR-432- 5 p/EMT轴抑制A549细胞的转移。
Ophiopogonin-B (OP-B) has been reported to suppress metastasis and angiogenesis of adenocarcinoma A549 cells in vitro and in vivo. More and more evidences indicate that inflammatory microenvironment facilitates tumor metastasis. Digital Gene Expression (DGE) analysis of non-small cell lung cancer (NSCLC) cell lines showed that OP-B downregulated the expression of linc00668, which promoted progression of cancer. Herein, we simulated the inflammatory microenvironment by co-culturing A549 cells with LPS-treated THP-1 cells and found that the level of linc00668 increased significantly in the mock group, while OP-B treatment inhibited the level of linc00668 and reversed epithelial-mesenchymal transition (EMT) induced by linc00668. In addition, overexpression of linc00668 in A549 cells suppressed the expression of E-cadherin and induced expression of N-cadherin, while OP-B treatment reversed these changes. Bioinformatic prediction and dual-luciferase reporter gene assay validated that linc00668 sponge miR-432-5p and at last acted on EMT to execute the anti-migration function of A549 cells under inflammatory microenvironment. Taken together, OP-B inhibits metastasis of A549 cells via the linc00668/miR-432-5p/EMT axis.