Wang Xinyu, Zhao Yue, Lu Qijue, Fei Xiang, Lu Chaojing, Li Chunguang, Chen Hezhong
Department of Thoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
J Cancer. 2020 Mar 4;11(10):3072-3081. doi: 10.7150/jca.39861. eCollection 2020.
: Our previous studies reported that lymphoid enhancer-binding factor 1 (LEF1) was upregulated in esophageal squamous cell carcinoma (ESCC) and the positive expression of LEF1 was correlated with aberrant clinicopathological characteristics in ESCC patients. However, the upstream mechanism of regulating LEF1 is not clear fully. In this study, we explored the role of miR-34a-5p in ESCC and the possible regulatory mechanism. : In this study, we applied western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), bioinformatics analysis, a luciferase reporter assay, and a series of functional assays to show the potential role of miR-34a-5p in regulating LEF1 in ESCC. : By various functional assays, we demonstrated that LEF1 promoted proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in ESCC cells. By bioinformatics analysis and luciferase reporter assay, miR-34a-5p was identified for directly targeting LEF1. Then we investigated the expression of miR-34a-5p and LEF1 in ESCC. As a result, miR-34a-5p was downregulated while LEF1 was upregulated in ESCC tissue and cell lines. Overexpression of miR-34a-5p could inhibit proliferation, migration, invasion and EMT of ESCC cells. The rescue experiment showed that re-expression of LEF1 reversed the suppressive effect caused by miR-34a-5p. At last, we found that miR-34a-5p could suppress Hippo-YAP1/TAZ signaling pathway in ESCC. : Our results indicate miR-34a-5p inhibits proliferation, migration, invasion and EMT in ESCC by targeting LEF1 and suppressing the Hippo-YAP1/TAZ signaling pathway, which may provide a new antitumor strategy to delay ESCC progress.
我们之前的研究报道，淋巴样增强因子1（LEF1）在食管鳞状细胞癌（ESCC）中上调，且LEF1的阳性表达与ESCC患者异常的临床病理特征相关。然而，调节LEF1的上游机制尚不完全清楚。在本研究中，我们探讨了miR-34a-5p在ESCC中的作用及可能的调控机制。：在本研究中，我们应用蛋白质免疫印迹法、定量实时聚合酶链反应（qRT-PCR）、生物信息学分析、荧光素酶报告基因检测以及一系列功能实验来展示miR-34a-5p在ESCC中调节LEF1的潜在作用。：通过各种功能实验，我们证明LEF1促进ESCC细胞的增殖、迁移、侵袭和上皮-间质转化（EMT）。通过生物信息学分析和荧光素酶报告基因检测，确定miR-34a-5p直接靶向LEF1。然后我们研究了ESCC中miR-34a-5p和LEF1的表达。结果显示，在ESCC组织和细胞系中，miR-34a-5p表达下调而LEF1表达上调。miR-34a-5p的过表达可抑制ESCC细胞的增殖、迁移、侵袭和EMT。挽救实验表明，LEF1的重新表达逆转了miR-34a-5p引起的抑制作用。最后，我们发现miR-34a-5p可抑制ESCC中的Hippo-YAP1/TAZ信号通路。：我们的结果表明，miR-34a-5p通过靶向LEF1并抑制Hippo-YAP1/TAZ信号通路来抑制ESCC的增殖、迁移、侵袭和EMT，这可能为延缓ESCC进展提供一种新的抗肿瘤策略。
