Abstract
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. 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. 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. 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.
Highlights
Bladder cancer is the fourth most common diagnosed malignancy, and is one of the most expensive malignancies to treatment in men worldwide [1]
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
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
Summary
Bladder cancer is the fourth most common diagnosed malignancy, and is one of the most expensive malignancies to treatment in men worldwide [1]. Increasing data have demonstrated that lncRNAs play a crucial role in modulating various cellular biological processes, including growth and differentiation, apoptosis, malignant metastasis, and epithelial-mesenchymal transition [8,9,10]. According to their location on the human genome, lncRNAs can be placed into five broad categories: sense, antisense, bidirectional, intronic, and intergenic. 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
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