The YAP1 oncogene contributes to bladder cancer cell proliferation and migration by regulating the H19 long noncoding RNA

Abstract

BackgroundYes-associated protein 1 (YAP1) and long noncoding RNA H19 act as potent oncogenes in many human cancers, but little is known about their roles in bladder cancer or their relationship with each other. MethodsQuantitative real-time polymerase chain reaction and western blotting were performed retrospectively on human bladder cancer specimens and on bladder cancer cell lines (UMUC-3, EJ, and 5637). YAP1 and H19 expression levels were detected and correlated with clinical and pathologic grades. To determine whether YAP1 regulates H19 expression, their genes were overexpressed or suppressed in 5637 and UMUC-3 cells. The effects of YAP1/H19 on proliferation and migration were determined by viability, colony formation, transwell migration, and wound-healing assays. ResultsYAP1 and H19 expression levels were markedly elevated in bladder cancer tissues and cells, and H19 expression was found to be significantly associated with YAP1 expression. Determination of their clinicopathologic significance in 40 human bladder cancer tissues showed that specimens in which YAP1 and H19 were overexpressed were associated with poorer clinicopathologic prognosis. In addition, YAP1 was found to enhance H19 expression, whereas H19 had no significant effect on YAP1 expression in bladder cancer cells. Furthermore, the results of in vitro analyses suggested that this association regulates cell proliferation and migration. ConclusionOur results emphasize the importance of YAP1 and H19 in bladder cancer progression and indicate that H19, at least in part, is induced by YAP1 overexpression.