Lu Yun, Liu Wei-Gang, Lu Jia-Hui, Liu Zhi Jun, Li Hai-Bin, Liu Gui-Jing, She Hong-Yan, Li Gui-Ying, Shi Xin-Hua
1 Department of Nephrology, The Affiliated Hospital of Hebei Engineering University, Handan, China.
2 Statistics Office, The Affiliated Hospital of Hebei Engineering University, Handan, China.
Tumour Biol. 2017 May;39(5):1010428317701632. doi: 10.1177/1010428317701632.
Long non-coding RNAs have recently emerged as important regulators in the pathogenesis and progression of cancers. The long non-coding RNA urothelial carcinoma-associated 1 is reportedly upregulated and functions as an oncogene in some tumors. However, the role of urothelial carcinoma-associated 1 in renal cell carcinoma is not well elucidated so far. In this study, we found that urothelial carcinoma-associated 1 was overexpressed in renal cell carcinoma tissues compared with the adjacent normal tissues, and higher urothelial carcinoma-associated 1 expression levels were positively associated with advanced tumor stage and poor survival time in renal cell carcinoma patients. Further studies showed that knockdown of urothelial carcinoma-associated 1 suppressed renal cell carcinoma cell proliferation and S-phase cell number in vitro. Moreover, urothelial carcinoma-associated 1 was found to be associated with enhancer of zeste homolog 2, which suppressed p21 expression through histone methylation (H3K27me3) on p21 promoter. We also showed that knockdown of urothelial carcinoma-associated 1 increased the p21 protein expression through regulating enhancer of zeste homolog 2. In addition, bioinformatics analysis and dual-luciferase reporter assays confirmed that miR-495 was a target of urothelial carcinoma-associated 1 in renal cell carcinoma, and urothelial carcinoma-associated 1 promoted cell proliferation by negatively regulating miR-495. These findings illuminated that urothelial carcinoma-associated 1 promoted renal cell carcinoma progression through enhancer of zeste homolog 2 and interacted with miR-495. Overall, overexpression of urothelial carcinoma-associated 1 functions as an oncogene in renal cell carcinoma that may offer a novel therapeutic target for renal cell carcinoma patients.
长链非编码RNA最近已成为癌症发病机制和进展中的重要调节因子。据报道，长链非编码RNA尿路上皮癌相关1在某些肿瘤中上调并发挥癌基因的作用。然而，尿路上皮癌相关1在肾细胞癌中的作用迄今尚未得到充分阐明。在本研究中，我们发现与相邻正常组织相比，尿路上皮癌相关1在肾细胞癌组织中过表达，并且较高的尿路上皮癌相关1表达水平与肾细胞癌患者的晚期肿瘤分期和较差的生存时间呈正相关。进一步的研究表明，敲低尿路上皮癌相关1可在体外抑制肾细胞癌细胞增殖和S期细胞数量。此外，发现尿路上皮癌相关1与zeste同源物2增强子相关，后者通过对p21启动子的组蛋白甲基化（H3K27me3）抑制p21表达。我们还表明，敲低尿路上皮癌相关1通过调节zeste同源物2增强子增加p21蛋白表达。此外，生物信息学分析和双荧光素酶报告基因检测证实miR-495是肾细胞癌中尿路上皮癌相关1的靶标，并且尿路上皮癌相关1通过负调节miR-495促进细胞增殖。这些发现表明，尿路上皮癌相关1通过zeste同源物2增强子促进肾细胞癌进展，并与miR-495相互作用。总体而言，尿路上皮癌相关1的过表达在肾细胞癌中发挥癌基因的作用，这可能为肾细胞癌患者提供新的治疗靶点。
