The YAP1 oncogene contributes to bladder cancer cell proliferation and migration by regulating the H19 long noncoding RNA
The YAP1 oncogene contributes to bladder cancer cell proliferation and migration by regulating the H19 long noncoding RNA
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DOI：
10.1016/j.urolonc.2015.06.003
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发表时间：
2015-10-01
影响因子：
2.7
通讯作者：
Tan, Wan-Long
中科院分区：
文献类型：
--
作者：
Li, Shi;Yu, Zhe;Tan, Wan-Long
背景：Yes 相关蛋白 1 (YAP1) 和长链非编码 RNA H19 在许多人类癌症中充当强效癌基因，但人们对它们在膀胱癌中的作用或彼此之间的关系知之甚少。方法：对人类膀胱癌标本和膀胱癌细胞系（UMUC-3、EJ 和 第5637章）检测YAP1和H19表达水平并与临床和病理分级相关。为了确定 YAP1 是否调节 H19 表达，它们的基因在 5637 和 UMUC-3 细胞中过度表达或抑制。通过活力、集落形成、Transwell迁移和伤口愈合实验来确定YAP1/H19对增殖和迁移的影响。结果：膀胱癌组织和细胞中YAP1和H19的表达水平显着升高，并且发现H19的表达与YAP1的表达显着相关。在 40 例人类膀胱癌组织中确定其临床病理学意义表明，YAP1 和 H19 过表达的标本与较差的临床病理预后相关。此外，YAP1被发现可以增强H19的表达，而H19对膀胱癌细胞中YAP1的表达没有显着影响。此外，体外分析结果表明这种关联调节细胞增殖和迁移。结论：我们的结果强调了 YAP1 和 H19 在膀胱癌进展中的重要性，并表明 H19 至少部分是由 YAP1 过表达诱导的。 (C) 2015 Elsevier Inc. 保留所有权利。
Background: Yes-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.Methods: Quantitative 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 overexpressecl 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.Results: YAP1 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.Conclusion: Our 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. (C) 2015 Elsevier Inc. All rights reserved.