Abstract
BackgroundAccumulating 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.MethodsThe 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.ResultsIn 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.ConclusionUCA1-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.
Highlights
Renal cell carcinoma (RCC) accounts for approximately 3% of all adult cancers, and poor survival is manifested in RCC patients, especially for those with metastasis [1]
We found that miR-182-5p mimics significantly inhibited luciferase activity of wild type reporter for long non-coding RNAs (lncRNAs)-Urothelial cancer associated 1 (UCA1), compared with the group of co-transfections with NC and pmirGLO-UCA1-Wt, the luciferase activity was decreased by 41.00% in 786–0(P < 0.001) and by 50.1% in Caki-1(P < 0.001) in the group of co-transfections with miR-182-5p mimics and pmirGLO-UCA1-Wt,miR-182-5p did not inhibit the luciferase activity of reporter vector containing the mutant binding sites of lncRNA-UCA1 (Fig. 6d)
The results showed that lncRNA-UCA1 pulled down with anti-Ago2 antibodies was significantly enriched in cells transfected with miR-182-5p mimics compared to controls. (Fig. 6e), suggesting that miR182-5p could directly target lncRNA-UCA1 in AGO2dependent manner
Summary
Renal cell carcinoma (RCC) accounts for approximately 3% of all adult cancers, and poor survival is manifested in RCC patients, especially for those with metastasis [1]. With the rapid development of sequencing technologies, a series of dysregulated long non-coding RNAs (lncRNAs) have been found in many human diseases, especially in cancers [2,3,4,5,6,7,8]. Accumulating evidences suggested that long non-coding RNAs (lncRNAs) perform important or vital functions in the malignant tumors [9,10,11,12,13,14,15]. 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. The molecular mechanism of UCA1 in renal cancer is still needed to further explore
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