A novel risk score model based on five angiogenesis-related long non-coding RNAs for bladder urothelial carcinoma

Abstract Background Tumour angiogenesis is an independent risk factor for bladder urothelial carcinoma (BUC) progression, but viable and promising antiangiogenic targets are understudied. Long non-coding RNAs (lncRNAs) have been reported to play significant roles in angiogenesis. Methods The clinical data of BUC patients were obtained from TCGA database and clinical specimens of 138 BUC patients. Angiogenesis-related long non-coding RNAs (ARLNRs) were extracted from The Molecular Signatures Database v4.0. Univariate and multivariate COX regression analyses were used to further identify survival-related ARLNRs (sARLNRs). A chain of techniques (FACS, western blotting, qPCR, immunohistochemistry, tube formation, migration and invasion assays) and co-culture models were utilized to validate the clinical significances and angiogenetic correlation of sARLNRs. Results Five sARLNRs were employed to establish angiogenesis-related risk score model, by which the patients in the low-risk group obtained longer overall survival than those in the high-risk group. Two sARLNRa in the risk score model (AC005625.1 and AC008760.1) expressed lower in BUC cell lines and tumour tissues than that in normal urothelial cells and adjacent normal tissues, with further lower expression in more advanced T stages. More importantly, the expression of AC005625.1 and AC008760.1 expression was negatively related to endothelial cells (ECs) percentage, tumour size and muscle invasion status. A prominently higher proportion of ECs was detected in tumour tissues with lower expression of AC005625.1 and AC008760.1. Furthermore, in the co-culture model of T24 cells and HUVEC cells, knockdown of AC005625.1 and AC008760.1 in BUC cells increased tube formation, migration and invasion abilities of HUVEC cells. The expression levels of CD31, VEGF-A, VIMENTIN and N-CADHERIN were also enhanced in HUVEC cells co-cultured with siR-AC005625.1 and siR-AC008760.1-treated T24 cells. Conclusion In the study, we identify five sARLNRs and validate their clinical significances, angiogenesis correlation and prognosis-predictive values in BUC. These results may provide a new perspective and some promising antiangiogenic targets for clinical diagnosis and treatment strategies of BUC.