BACKGROUND Accumulating literatures have indicated that long non-coding RNAs (lncRNAs) are potential biomarkers that play key roles in tumor development and progression. Urothelial cancer associated 1 (UCA1) is a novel lncRNA that acts as a potential biomarker and is involved in the development of cancers. However, the molecular mechanism of UCA1 in renal cancer is still needed to further explore. METHODS The relative expression level of UCA1 was determined by Real-Time qPCR in a total of 88 patients with urothelial renal cancer and in different renal cancer cell lines. Loss-of-function experiments were performed to investigate the biological roles of UCA1 and miR-182-5p on renal cancer cell proliferation, migration, apoptosis and tumorigenicity. Comprehensive transcriptional analysis, dual-luciferase reporter assay and western blot etc. were performed to explore the molecular mechanisms underlying the functions of UCA1. RESULTS In this study, we found that UCA1 was significantly up-regulated in renal cancer. Moreover, increased UCA1 expression was positively correlated with differentiation and advanced TNM stage. Further experiments demonstrated that knockdown of UCA1 inhibited malignant phenotypes and Notch signal path of renal cancer cells, and miR-182-5p was reverse function as UCA1. UCA1 functioned as a miRNA sponge to positively regulate the expression of Delta-like ligand 4(DLL4) through sponging miR-182-5p and subsequently promoted malignant phenotypes of renal cancer cells, thus UCA1 playing an oncogenic role and miR-182-5p as an antioncogenic one in renal cancer pathogenesis. CONCLUSION UCA1-miR-182-5p-DLL4 axis is involved in proliferation and progression of renal cancer. Thus, this study demonstrated that UCA1 plays a critical regulatory role in renal cancer cell and UCA1 may serve as a potential diagnostic biomarker and therapeutic target of renal cancer.

中文翻译：

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长链非编码 RNA UCA1 通过调节 miR-182-5p/DLL4 轴作为 ceRNA 促进肾癌细胞的恶性表型。

背景 越来越多的文献表明，长链非编码RNA（lncRNA）是潜在的生物标志物，在肿瘤的发生和发展中起关键作用。尿路上皮癌相关 1 (UCA1) 是一种新型 lncRNA，可作为潜在的生物标志物并参与癌症的发展。但UCA1在肾癌中的分子机制仍需进一步探索。方法通过Real-Time qPCR测定88例尿路上皮肾癌患者和不同肾癌细胞系中UCA1的相对表达水平。进行功能丧失实验以研究 UCA1 和 miR-182-5p 对肾癌细胞增殖、迁移、凋亡和致瘤性的生物学作用。综合转录分析、双荧光素酶报告基因检测和蛋白质印迹等。进行了探索UCA1功能的分子机制。结果在本研究中，我们发现UCA1在肾癌中显着上调。此外，增加的UCA1表达与分化和晚期TNM分期呈正相关。进一步的实验表明，敲低UCA1可抑制肾癌细胞的恶性表型和Notch信号通路，而miR-182-5p与UCA1的功能相反。UCA1作为miRNA海绵发挥作用，通过海绵化miR-182-5p正向调节Delta样配体4（DLL4）的表达，从而促进肾癌细胞的恶性表型，从而UCA1发挥致癌作用，miR-182-5p作为肾癌发病机制中的抗癌剂。结论 UCA1-miR-182-5p-DLL4轴参与肾癌的增殖和进展。因此，本研究表明UCA1在肾癌细胞中起着关键的调节作用，UCA1可能作为肾癌的潜在诊断生物标志物和治疗靶点。