PDF(Pubmed)
Abstract：
Long non-coding RNAs (lncRNAs) have been implicated in the progression and development of many types of cancer by interacting with RNA, DNA and proteins, including DLEU7-AS1. However, the function of DLEU7-AS1 in renal cell cancer (RCC) remains unclear. In this study, two in silico prediction algorithms were used to discover the potential target of miR-26a-5p, which was determined to be a tumor suppressor gene, possibly DLEU7-AS1, through the downregulation of coronin-3 in RCC. Thus, we hypothesized that DLEU7-AS1 promotes RCC by silencing the miR-26a-5p/coronin-3 axis. To test our hypothesis, we confirmed that DLEU7-AS1 directly targets miR-26a-5p using the pmirGLO dual-luciferase reporter assay. Next, we observed that DLEU7-AS1 expression was markedly upregulated in RCC samples and inversely correlated with clinical prognosis and miR-26a-5p levels. Knockdown of DLEU7-AS1 significantly suppressed the growth and metastasis of RCC cells in vitro and attenuated tumor growth in vivo. Interestingly, exogenous expression of coronin-3 or miR-26a-5p inhibitor treatment almost completely rescued the DLEU7-AS1 knockdown-induced inhibitory effects on cell proliferation, migration and invasion. In conclusion, our data demonstrate that DLEU7-AS1 is an oncogene in RCC capable of regulating the growth and metastasis of RCC by silencing the miR-26a-5p/coronin-3 axis, suggesting that DLEU7-AS1 can be employed as a potential therapeutic target and prognostic biomarker for RCC.
摘要：
长链非编码RNA（lncRNA）通过与RNA相互作用而参与许多类型癌症的进展和发展。DNA和蛋白质,包括DLEU7-AS1。然而,DLEU7-AS1在肾细胞癌(RCC)中的作用尚不清楚.在这项研究中,使用两种计算机预测算法来发现miR-26a-5p的潜在靶标，被确定为肿瘤抑制基因，可能是DLEU7-AS1，通过下调RCC中的coronin-3。因此，我们假设DLEU7-AS1通过沉默miR-26a-5p/coronin-3轴促进RCC.为了检验我们的假设,我们使用pmirGLO双荧光素酶报告基因试验证实DLEU7-AS1直接靶向miR-26a-5p.接下来,我们观察到DLEU7-AS1表达在RCC样本中显著上调,并与临床预后和miR-26a-5p水平呈负相关.DLEU7-AS1的敲除在体外显着抑制了RCC细胞的生长和转移，并在体内减弱了肿瘤的生长。有趣的是,外源表达的coronin-3或miR-26a-5p抑制剂治疗几乎完全挽救了DLEU7-AS1敲低诱导的细胞增殖抑制作用，移民和入侵。总之,我们的数据表明DLEU7-AS1是RCC中的癌基因，能够通过沉默miR-26a-5p/coronin-3轴来调节RCC的生长和转移，提示DLEU7-AS1可作为RCC的潜在治疗靶点和预后生物标志物。
