Long non-coding RNA DLEU2 promotes the progression of esophageal cancer through miR-30e-5p/E2F7 axis
Long non-coding RNA DLEU2 promotes the progression of esophageal cancer through miR-30e-5p/E2F7 axis
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DOI：
10.1016/j.biopha.2019.109650
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发表时间：
2020-03-01
影响因子：
7.5
通讯作者：
Cui, Youbin
中科院分区：
文献类型：
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作者：
Lu, Tianyu;Wang, Rui;Cui, Youbin
背景：越来越多的证据证明lncrna在肿瘤发生和肿瘤生物学中的重要作用。然而，lncRNA DLEU2在食管癌（食管癌）进展中的作用尚未阐明。在本研究中，我们旨在探讨lncRNA DLEU2对EC进展的影响及其潜在机制。方法：本研究在EC细胞系Eca-109和KYSE-150中，通过siRNA干扰使lncRNA DLEU2沉默，通过转染pcDNA3.1-DLEU2，使其在TE-1细胞中表达上调，并检测其生物学功能。然后利用生物信息学分析和双荧光素酶报告基因法鉴定lncRNA DLEU2的结合miRNA和miRNA的靶基因。此外，进行功能丧失测定以检测靶基因的生物学功能。最后，采用拯救法研究lncRNA、DLEU2、miRNA与靶基因之间的关系。结果：通过GEPIA分析，我们发现lncRNA DLEU2在EC组织中表达上调，且与预后不良相关。功能缺失实验表明，沉默lncRNA DLEU2可抑制EC细胞的增殖、迁移和侵袭，并通过调节Bcl-2/Bax轴和Caspase级联诱导凋亡。lncRNA DLEU2的过表达增加了TE-1细胞的增殖、迁移和侵袭能力，减少了细胞凋亡。生物信息学分析和双荧光素酶报告基因实验证实，miR-30e-5p可以直接与lncRNA DLEU2结合，E2F7是EC细胞中miR-30e-5p的直接靶点。此外，我们的数据显示，沉默E2F7可降低EC细胞的增殖、迁移和侵袭能力，并诱导凋亡。此外，挽救实验表明，miR-30e-5p抑制剂或上调E2F7可逆转lncRNA DLEU2对EC细胞增殖、迁移和侵袭的影响。结论：我们的研究结果揭示了lncRNA DLEU2和E2F7在EC进展中的促癌作用，提示lncRNA DLEU2通过调节miR-30e-5p/E2F7轴在EC中发挥ceRNA功能。
Background: Emerging evidences have proven the important roles of lncRNAs in tumorigenesis and cancer biology. However, the function of lncRNA DLEU2 in the progression of esophageal cancer (EC) has not been elaborated. In the present study, we aimed to investigate the effects of lncRNA DLEU2 on the progression of EC and the underlying mechanism.Methods: In this study, lncRNA DLEU2 was silenced by siRNA interference in EC cell lines Eca-109 and KYSE-150, and its expression was up-regulated in TE-1 cells by transfection with pcDNA3.1-DLEU2, and its biological functions were examined. Then, bioinformatics analysis and dual-luciferase reporter assay were used to identify the binding miRNA of lncRNA DLEU2 and the target gene of miRNA. In addition, loss-of-function assays were performed to detect the biological functions of the target gene. At last, the rescue assays were used to investigate the relationship among lncRNA DLEU2, miRNA and target gene.Results: With the help of GEPIA analysis, we observed that lncRNA DLEU2 was up-regulated in EC tissues and associated with poor prognosis. Loss-of-function assay showed that silencing lncRNA DLEU2 inhibited the proliferation, migration and invasion of EC cells, and induced apoptosis by regulating the Bcl-2/Bax axis and Caspase cascade. Overexpression of lncRNA DLEU2 increased the proliferation, migration and invasion abilities of TE-1 cells, as well as decreased cell apoptosis. Bioinformatics analysis and dual-luciferase reporter assay verified that miR-30e-5p could directly bind with lncRNA DLEU2, and E2F7 was a direct target for miR-30e-5p in EC cells. Moreover, our data revealed that silencing E2F7 decreased the proliferation, migration and invasion abilities of EC cells, and induced apoptosis. Furthermore, the rescue assays demonstrated that the effects of lncRNA DLEU2 on the proliferation, migration and invasion of EC cells were reversed by miR-30e-5p inhibitor or up-regulation of E2F7.Conclusions: Our findings revealed the pro-oncogenic role of lncRNA DLEU2 and E2F7 in the progression of EC, suggesting that lncRNA DLEU2 exerts ceRNA functions in EC through regulating miR-30e-5p/E2F7 axis.