Stem cell associated IncRNA promotes the self-renewal in bladder cancer stem cells and acts as a predictor for recurrence of bladder cancer / 中华泌尿外科杂志

ABSTRACT

Objective To investigate the expression profile and biological function of lncRNAs in urothelial cancer stem cells and explore whether they can be biomarkers for prediction of clinical characteristics for bladder cancer patients.Methods Microarray analysis was performed to identify differentially expressed lncRNAs in cancer stem cells and parental cancer cells.Expression profiles were validated by Coding Potential Caculator analysis,real-time polymerase chain reaction.By performing in vitro sphere formation assays,J82 cells with lentivirus-based knockdown of lncRNA-BCSC (bladder cancer stem cells) were used to confirmed its function.Samples were obtained from patients who underwent TURBT between January 2009 and December 2012.All tissues were initially confirmed by pathologists.The association of the clinicpathologic of bladder cancer and lncRNA-BCSC expression was analyzed by x2 analysis.Results 750 lncRNAs were highly expressed from microarray analysis in bladder cancer stem cells.Among these,lncRNA-BCSC was identified as potentially maintaining self-renewal of cancer stem cells.Knockdown of this transcript in J82 cells inhibited spheroid formation.lncRNA-BCSC expression were higher in 54.8％ (57/104) bladder cancer tissues.Moreover,using x2 analysis,lncRNA-BCSC expression in primary tumors was found to be a predictor for recurrence following transurethral resection in patients with nonmuscle-invasive bladder cancer (P =0.009).Conclusions Our study provides strong evidence that lncRNA-BCSC are indispensable modulators of self-renewal ability of bladder cancer stem cells.Overexpression of lncRNA-BCSC may have a predictive value for early recurrence in patients suffering from nonmuscle-invasive bladder cancer.