Upregulation of long non-coding RNA ROR1-AS1 promotes cell growth and migration in bladder cancer by regulation of miR-504.

BACKGROUND:Increasing evidence has suggested that multiple long non-coding RNAs (lncRNAs) act key regulatory functions in the pathogenesis of bladder cancer. This study aimed to determine the expression and clinical significance of lncRNA ROR1 antisense RNA 1 (ROR1-AS1) from patients with bladder cancer, and to explore the potential role and mechanism underlying ROR1-AS1-related cancer progression. METHODS:Real time quantitative PCR (RT-qPCR) was conducted to detected the expression levels of ROR1-AS1 and miR-504 in bladder cancer samples and cell lines. Chi-square test was used for correlation analysis. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and wound scratch assays were applied to assesses the effects of ROR1-AS1 overexpression and knockdown on bladder cancer cell growth and migration in vitro, respectively. The prognosis of bladder cancer patients was evaluated by survival curves with Kaplan-Meier method. The regulatory mechanism of ROR1-AS1 on miR-504 was confirmed by bioinformatics analysis and luciferase reporter gene assay. RESULTS:ROR1-AS1 levels were obviously upregulated in bladder cancer tissues than matched normal bladder tissues. High expression of ROR1-AS1 was remarkably correlated with higher histological grade, advanced tumor stage, and positive lymph node metastasis. High ROR1-AS1 expression was markedly correlated with shorter overall survival of bladder cancer patients. Moreover, knockdown of ROR1-AS1 notably repressed T24 and 5637 cell growth and migration. ROR1-AS1 directly bound with miR-504 and act as a molecular sponge to decrease miR-504 expression. Silencing of miR-504 partly abrogated ROR1-AS1 knockdown-induced inhibitory effects on bladder cancer cell growth and migration. CONCLUSIONS:Our data demonstrated that increased ROR1-AS1 promotes cell growth and migration of bladder cancer via regulation of miR-504, indicating ROR1-AS1 may be used as a prognostic biomarker and therapeutic target for bladder cancer.

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