Downregulation of UBAP2L Inhibits the Epithelial-Mesenchymal Transition via SNAIL1 Regulation in Hepatocellular Carcinoma Cells
Downregulation of UBAP2L Inhibits the Epithelial-Mesenchymal Transition via SNAIL1 Regulation in Hepatocellular Carcinoma Cells
复制标题
肝细胞癌细胞中 UBAP2L 的下调通过 SNAIL1 调节抑制上皮间质转化
DOI：
10.1159/000470824
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发表时间：
2017-01-01
影响因子：
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通讯作者：
Xia, Jinglin
中科院分区：
文献类型：
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作者：
Ye, Tao;Xu, Jing;Xia, Jinglin
背景/目的：据报道，肿瘤中存在泛素相关蛋白 2 样 (UBAP2L) 失调，但其在肝细胞癌 (HCC) 进展中的作用尚不清楚。方法：通过蛋白质印迹和实时定量（qRT）PCR检测肝癌组织和肝癌细胞系中UBAP2L的表达水平。通过伤口愈合实验和基质胶transwell实验研究UBAP2L表达对HCC细胞生物学特性（包括迁移和侵袭）的影响。同时采用Western blot和qRT-PCR检测E-cadherin、CK-18、N-cadherin、Vimentin、Claudin7等上皮间质转化（EMT）标志物的表达及E-cadherin启动子活性。随后，进一步研究了SNAIL1在UBAP2L介导的EMT中的作用以及UBAP2L介导的SNAIL1表达的机制。结果：与瘤周组织相比，UBAP2L 在人 HCC 组织中过表达。 UBAP2L 的下调抑制高度转移性 HCC 细胞系的迁移、侵袭和 EMT。此外，UBAP2L 敲低抑制转录阻遏蛋白 SNAIL1 的表达及其通过 SMAD2 信号通路与 E-钙粘蛋白启动子结合的能力，从而导致 E-钙粘蛋白表达增加。此外，生物信息学分析表明UBAP2L的表达与HCC患者的不良预后相关。结论：UBAP2L 通过 SNAIL1 调节在维持 HCC 细胞的转移能力中发挥着关键作用，并且预示着不良的临床结果。
Background/Aims: Dysregulation of ubiquitin-associated protein 2-like (UBAP2L) has been reported in tumors, but its role in hepatocellular carcinoma (HCC) progression is unclear. Methods: The expression levels of UBAP2L in HCC tissues and HCC cell lines were detected by western blot and quantitative real-time (qRT) PCR. The effects of UBAP2L expression on HCC cell biological traits, including migration and invasion, were investigated by wound healing assay and matrigel transwell assay. Simultaneously, the expression of epithelial-mesenchymal transition (EMT) markers including E-cadherin, CK-18, N-cadherin, Vimentin, Claudin7 and the promoter activity of E-cadherin were detected by western blot and qRT-PCR. Subsequently, role of SNAIL1 in UBAP2L-mediated EMT and the mechanism underlying UBAP2L-mediated SNAIL1 expression were further investigated. Results: UBAP2L was overexpressed in human HCC tissues compared with peri-tumoral tissues. Downregulation of UBAP2L inhibited migration, invasion and the EMT in highly metastatic HCC cell lines. Furthermore, UBAP2L knockdown inhibited expression of the transcriptional repressor SNAIL1 and its ability to bind to the E-cadherin promoter via SMAD2 signaling pathway, which in turn resulted in increased E-cadherin expression. Additionally, bioinformatics analysis showed that expression of UBAP2L is correlated with poor prognosis in patients with HCC. Conclusions: UBAP2L plays a critical role in maintenance of the metastatic ability of HCC cells via SNAIL1 Regulation and is predictive of a poor clinical outcome.