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 carcinomaassociated 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.
KeywordsRenal cell carcinoma, urothelial carcinoma-associated 1, enhancer of zeste homolog 2, miR-495, tumor proliferation Long non-coding RNAs (lncRNAs), that are more than 200 bases in length, consist of exons and introns in structure, without ORFs, and are not highly conserved. Recent reports suggest that lncRNAs play an important role in regulation of diverse cellular processes such as cell growth and apoptosis and cancer metastasis. 5 Several lncRNAs have been reported to be participated in renal cancer, such as, Qiao et al. 6 found that a decrease in lncRNA growth arrest-specific 5 (GAS5) expression was associated with RCC genesis and progression and overexpression of GAS5 can inhibit the RCC progression. A recent study indicated that LncRNA metastasis-associated lung adenocarcinoma transcription 1 (MALAT1) could function as a competing endogenous RNA to regulate zinc finger e-box binding homeobox 2 (ZEB2) expression by sponging miR-200s in clear cell kidney carcinoma. 7 HOX transcript antisense RNA (HOTAIR) was overexpressed in RCC, and knockdown of HOTAIR led to the weakening of the recruitment and binding abilities of enhancer of zeste homolog 2 (EZH2) and H3K27me3 locus with lncRNA HOTAIR and inhibited cell prol...