Department of Pediatrics, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China.
Cancer Institute, Henan University of Science and Technology, Luoyang, China.
J Cell Biochem. 2018 Dec;119(12):9694-9706. doi: 10.1002/jcb.27284. Epub 2018 Aug 21.
Recently, long noncoding RNAs (lncRNAs) have captured much attention for their important roles in human diseases. Deregulation of lncRNA taurine-upregulated gene 1 (TUG1) has been reported to regulate cancer progression in many cancer types. However, how TUG1 contributes to renal cell carcinoma (RCC) remains elusive; we were eager to resolve the questions.
Tumor tissues and the matched adjacent normal tissues were collected from patients with RCC. Messenger RNA (mRNA) levels of TUG1, yes-associated protein (YAP), and microRNA (miR)-9 levels were determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR). The regulation of YAP by TUG1 was investigated using Western blot analysis, RT-qPCR, and immunofluorescence. The oncogenic roles of TUG1 and YAP were studied using a cell proliferation assay and a wound healing assay. The interaction of TUG1-miR-9-YAP was analyzed in RCC cell lines.
In the current study, we observed a positive correlation between TUG1 expression and YAP expression in RCC using the Gene Expression Omnibus database and tumor tissues collected from 58 patients with RCC. The TUG1 elevation enhanced YAP expression but did not alter the Hippo-signaling pathway activity or YAP protein distribution in cells. In addition, we found that TUG1 could bind to miR-9; therefore, TUG1 could positively control YAP expression via downregulation of miR-9 level. Furthermore, we observed that inhibition of cell proliferation and cell migration induced by TUG1 silencing could be reversed by overexpression of YAP in RCC cell lines.
Our findings indicated a pivotal role of TUG1 in driving RCC progression via regulation of miR-9/YAP, suggesting a potential therapeutic targeting role of TUG1 in RCC.
长链非编码 RNA（lncRNA）因其在人类疾病中的重要作用而备受关注。已有报道称，tRNA 上调基因 1（TUG1）的失调可调节多种癌症类型的癌症进展。然而，TUG1 如何促进肾细胞癌（RCC）的发展仍不清楚；我们渴望解决这些问题。
收集 RCC 患者的肿瘤组织和相应的相邻正常组织。采用逆转录定量聚合酶链反应（RT-qPCR）测定 TUG1、yes 相关蛋白（YAP）和 microRNA（miR）-9 的信使 RNA（mRNA）水平。采用 Western blot 分析、RT-qPCR 和免疫荧光法研究 TUG1 对 YAP 的调节作用。通过细胞增殖试验和划痕愈合试验研究 TUG1 和 YAP 的致癌作用。在 RCC 细胞系中分析 TUG1-miR-9-YAP 的相互作用。
本研究通过基因表达综合数据库和 58 例 RCC 患者的肿瘤组织观察到 RCC 中 TUG1 表达与 YAP 表达呈正相关。TUG1 升高增强了 YAP 表达，但不改变细胞中 Hippo 信号通路活性或 YAP 蛋白分布。此外，我们发现 TUG1 可以与 miR-9 结合；因此，TUG1 可以通过下调 miR-9 水平来正向控制 YAP 表达。此外，我们观察到 TUG1 沉默抑制细胞增殖和迁移的作用可以被 RCC 细胞系中转染的 YAP 过表达逆转。
我们的研究结果表明，TUG1 通过调节 miR-9/YAP 在推动 RCC 进展中起着关键作用，提示 TUG1 在 RCC 中具有潜在的治疗靶向作用。
