Department of Urology, the First Affiliated Hospital of Soochow University, Suzhou, China.
Department of Urology, the First Hospital in Changzhou, Changzhou, China.
J Cell Biochem. 2019 Jun;120(6):10821-10829. doi: 10.1002/jcb.28373. Epub 2019 Jan 22.
Bladder cancer is the most common malignancy with high recurrence. Currently, the long noncoding RNAs (lncRNAs) have been suggested to play vital roles in the pathogenesis of bladder cancer. The present study investigated the role of lncRNA MIR503 host gene (MIR503HG) in the pathogenesis of bladder cancer by using both in vitro and in vivo functional assays. The expression of MIR503HG was downregulated in bladder cancer tissues and cell lines. Low expression of MIR503HG was associated with advanced tumor stage, advanced histological grade, and lymph node metastasis. Ectopic expression of MIR503HG inhibited cell proliferation, cell growth, cell invasion, and migration, and also promoted cell apoptosis and inhibited cell cycle progression in SW780 cells. In parallel, T24 cells were used for loss-of-function studies. Knockdown of MIR503HG promoted the cancer cell proliferation and increased the migration and invasion abilities of T24 cells. In addition, knockdown of MIR503HG reduced the cell apoptotic rate in cancer cells and promoted cell cycle progression. Furthermore, MIR503HG overexpression decreased the epithelial-mesenchymal transition-related mRNA and protein levels of ZEB1, Snail, N-cadherin, and vimentin, with an increase in E-cadherin level. Consistently, knockdown of MIR503HG showed the opposite effects. In vivo xenograft, nude mice results showed that overexpression of MIR503HG suppressed the tumor growth and tumor metastasis. In conclusion, our results identified a novel lncRNA MIR503HG that exhibited significant antiproliferation, antimigration/invasion effects on bladder cancer cells both in vitro and in vivo, which may hold a therapeutic promise to treat bladder cancer.
膀胱癌是最常见的恶性肿瘤，具有较高的复发率。目前，长链非编码 RNA（lncRNA）被认为在膀胱癌的发病机制中发挥重要作用。本研究通过体外和体内功能测定，探讨了 lncRNA MIR503 宿主基因（MIR503HG）在膀胱癌发病机制中的作用。MIR503HG 在膀胱癌组织和细胞系中表达下调。MIR503HG 低表达与肿瘤分期较晚、组织学分级较高、淋巴结转移有关。在 SW780 细胞中异位表达 MIR503HG 可抑制细胞增殖、细胞生长、细胞侵袭和迁移，并促进细胞凋亡，抑制细胞周期进程。同时，使用 T24 细胞进行功能缺失研究。敲低 MIR503HG 促进了癌细胞的增殖，并增加了 T24 细胞的迁移和侵袭能力。此外，敲低 MIR503HG 降低了癌细胞的细胞凋亡率并促进了细胞周期进程。此外，MIR503HG 过表达降低了 ZEB1、Snail、N-钙粘蛋白和波形蛋白的上皮-间充质转化相关 mRNA 和蛋白水平，同时增加了 E-钙粘蛋白水平。一致地，敲低 MIR503HG 表现出相反的效果。体内异种移植裸鼠结果表明，MIR503HG 的过表达抑制了肿瘤的生长和转移。总之，我们的研究结果确定了一种新的 lncRNA MIR503HG，它在体外和体内对膀胱癌细胞具有显著的抗增殖、抗迁移/侵袭作用，可能为治疗膀胱癌提供了一种有希望的治疗方法。
