ncRAN, a Newly Identified Long Noncoding RNA, Enhances Human Bladder Tumor Growth, Invasion, and Survival

OBJECTIVES To study the functional significance of ncRAN, a newly identified long noncoding RNA, expression in bladder cancer growth, invasion, and survival. METHODS Expression of ncRAN isoforms was analyzed by reverse transcription-polymerase chain reaction in 40 clinical specimens and four bladder cancer cell lines, respectively. The expression of ncRAN in the clinical specimens was correlated to clinical stage or grade to assess for potential relationship. ncRAN-long form or ncRAN-short form was stably overexpressed in human bladder cancer cell line, RT4(superficial) exhibiting low endogenous expression of ncRAN, respectively. The influence of ncRAN on cancer cell survival was evaluated by silencing with short hairpin RNA in 5637 cells (invasive). Functional assays were performed to study the resulting changes in cell proliferation, motility, invasion, and survival. RESULTS Expression of ncRAN was significantly higher in bladder cancers compared with normal tissues (P < .01) and in invasive tumor compared with superficial ones (P < .01). Consistently, ncRAN expressed significantly higher in invasive bladder tumor cell lines (5637, T24, J82) than that in superficial tumor cell line (RT4). Overexpression of ncRAN in RT4 cells significantly enhanced cell proliferation, migration, and invasion. Silencing of ncRAN improved chemotherapy sensitivity in 5637 cells. CONCLUSIONS Our clinical and experimental data suggest that ncRAN may play an important role in the pathogenesis of human bladder cancer, and may help in designing effective therapy targeting the ncRAN pathway to control bladder cancer growth and invasion. UROLOGY 77: 510.e1-510.e5, 2011. (C) 2011 Elsevier Inc.