Zhang Beilin, Fang Shaokuan, Cheng Yingying, Zhou Chunkui, Deng Fang
Department of Neurology, The First Teaching Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Aging (Albany NY). 2019 Oct 8;11(19):8239-8253. doi: 10.18632/aging.102317.
The long non-coding RNA, urothelial carcinoma associated 1 (UCA1) has been demonstrated to play important roles in various types of cancers. This study investigated the functional role of UCA1 in glioma and explored the underlying molecular mechanisms. UCA1 was found to be highly up-regulated in glioma cells, and knock-down of UCA1 inhibited cell growth, invasion and migration, and also induced apoptosis in glioma cells. On the other hand, overexpression of UCA1 promoted cell proliferation, cell invasion and migration in glioma cells. Knock-down of UCA1 suppressed the activity of Wnt/β-catenin signaling, and treatment with lithium chloride restored the inhibitory effect of UCA1 knock-down on cell invasion and migration. More importantly, the aberrant expression of UCA1 was associated with chemo-resistance to cisplatin and temozolomide in glioma cells via interacting with Wnt/β-catenin signaling. studies showed that overexpression of UCA1 promoted the tumor growth of U87 cells in the nude mice. Clinically, UCA1 was found to be up-regulated in glioma tissues and higher expression level of UCA1 was correlated with poor survival in patients with glioma. Taken together, our results showed that UCA1 had a functional role in the regulation of glioma cell growth, invasion and migration, and chemo-resistance possibly via Wnt/β-catenin signaling pathway.
长链非编码RNA,尿路上皮癌相关1(UCA1)已被证明在各种类型的癌症中发挥重要作用。本研究调查了UCA1在胶质瘤中的功能作用,并探讨了其潜在的分子机制。研究发现UCA1在胶质瘤细胞中高度上调,敲低UCA1可抑制细胞生长、侵袭和迁移,并诱导胶质瘤细胞凋亡。另一方面,UCA1的过表达促进了胶质瘤细胞的增殖、侵袭和迁移。敲低UCA1可抑制Wnt/β-连环蛋白信号通路的活性,用氯化锂处理可恢复敲低UCA1对细胞侵袭和迁移的抑制作用。更重要的是,UCA1的异常表达通过与Wnt/β-连环蛋白信号通路相互作用,与胶质瘤细胞对顺铂和替莫唑胺的化疗耐药性相关。研究表明,UCA1的过表达促进了裸鼠中U87细胞的肿瘤生长。临床上,发现UCA1在胶质瘤组织中上调,UCA1的高表达水平与胶质瘤患者的不良生存相关。综上所述,我们的结果表明,UCA1可能通过Wnt/β-连环蛋白信号通路在调节胶质瘤细胞生长、侵袭、迁移和化疗耐药性方面发挥功能作用。