LncRNA H19 promotes epithelial mesenchymal transition and metastasis of esophageal cancer via STAT3/EZH2 axis
LncRNA H19 promotes epithelial mesenchymal transition and metastasis of esophageal cancer via STAT3/EZH2 axis
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DOI：
10.1016/j.biocel.2019.05.011
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发表时间：
2019-08-01
影响因子：
4
通讯作者：
Xia, Zhen-Kun
中科院分区：
文献类型：
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作者：
Chen, Ming-Jiu;Deng, Jie;Xia, Zhen-Kun
背景：长链非编码RNAH19 （lncRNA H19）在食管癌（EC）中已被广泛报道，既往研究发现lncRNAH19在食管癌中上调表达，促进细胞增殖和转移。但其作用机理仍需进一步研究。方法：采用qRT-PCR方法分析30例患者匹配样本中lncRNA H19的表达水平。利用qRT-PCR和western blotting检测5株EC细胞株中lncRNA H19、let-7、STAT3和EZH2的表达水平。在体外采用MIT法、集落形成法、Transwell法和流式细胞术检测lncRNA H19对细胞系细胞增殖、迁移、侵袭和凋亡的影响，在体内采用异种移植裸鼠模型检测肿瘤形成。采用qRT-PCR和western blotting检测STAT3、EZH2、β -catenin以及E-cadherin、N-cadherin、Snail-1、MMP-9等EMT及转移相关分子的表达水平。最后，利用荧光素酶报告基因法和RIP法验证lncRNA H19与let-7c之间的相互作用，以及它们随后对STAT3的调控。结果：敲低lncRNA H19可通过STAT3- ezh2 - β -catenin通路抑制细胞增殖、迁移侵袭及EMT和转移，而lncRNA H19调控STAT3可负调控EC细胞株的let-7c。结论：lncRNA H19通过let-7c/STAT3/EZH2/ β -catenin轴促进EC的EMT和转移。
Background: Long non-coding RNA H19 (lncRNA H19) has been widely reported in esophageal cancer (EC), and previous study had found that lncRNAH19 was up-regulated in EC and promoted cell proliferation and metastasis. However, the mechanism still needs further studied.Methods: Levels of lncRNA H19 were analyzed by qRT-PCR in matched samples from 30 patients. Expression levels of lncRNA H19, let-7, STAT3 and EZH2 were additionally identified by qRT-PCR and western blotting in five EC cell lines. The effects of lncRNA H19 on cell proliferation, migration, invasion and apoptosis in cell lines were performed by MIT assay, colony formation assay, Transwell assay and flow cytometry in vitro, and tumor formation was detected by xenograft nude mice model in vivo. The expression level of STAT3, EZH2,beta-catenin, and EMT and metastasis related molecules such as E-cadherin, N-cadherin, Snail-1 and MMP-9 was assessed by qRT-PCR and western blotting. Finally, luciferase reporter assay and RIP assay were used to verify the interaction between lncRNA H19 and let-7c, and their subsequent regulation of STAT3.Results: Knockdown of lncRNA H19 repressed cell proliferation, migration and invasion as well as EMT and metastasis via STAT3-EZH2-beta-catenin pathway, while lncRNA H19 regulated STAT3 negatively regulated let-7c in EC cell lines.Conclusions: lncRNA H19 facilitates EMT and metastasis of EC through let-7c/STAT3/EZH2/beta-catenin axis.