Department of Urology, East Hospital, Tongji University School of Medicine, Shanghai, 200123, China.
Department of Urology, East Hospital, Ji'an Hospital, Jiangxi 343000, China.
Biomed Pharmacother. 2018 Jul;103:174-181. doi: 10.1016/j.biopha.2018.04.031. Epub 2018 Apr 24.
The incidence and mortality rate of bladder cancer have dramatically expanded, so it's urgent to discover new biomarker and therapeutic target for bladder cancer. Recently, lncRNA has been identified as oncogene or tumor suppressor to regulate the tumorigenesis. LncRNA ZFAS1 has been confirmed as oncogene in various tumors. However, the expression, function, and underlying mechanism of ZFAS1 in bladder carcinogenesis have yet to be totally clarified. In the current study, our data demonstrated that ZFAS1 expression was significantly upregulated in bladder cancer tissues and cell lines. Furthermore, Kaplan-Meier analysis revealed that high ZFAS1 expression was significantly associated with unfavorable progression free survival (PFS) (P = 0.0034 < 0.01) and overall survival (OS) (P = 0.0041 < 0.01) of bladder cancer patients. Moreover, silencing of ZFAS1 expression could markedly suppress bladder cancer cells proliferation and colony formation, arrest cell cycle, promote cell apoptosis and inhibit cell migration in vitro. In addition, bioinformatics analysis, luciferase reporter assay, and pull down assay revealed that ZFAS1 straightly interacted with miR-329. Lastly, rescue experiments confirmed that miR-329 inhibitor reversed the tumor suppressing roles of ZFAS1 knockdown on bladder cancer cells. Collectively, our results illuminated that ZFAS1 could serve as an oncogene in the tumorigenesis of bladder cancer, and discovered the functional regulatory network of ZFAS1 sponging miR-329.
膀胱癌的发病率和死亡率显著上升,因此迫切需要发现膀胱癌的新生物标志物和治疗靶点。最近,lncRNA 被鉴定为癌基因或肿瘤抑制因子,调节肿瘤发生。lncRNA ZFAS1 已被证实为多种肿瘤的癌基因。然而,ZFAS1 在膀胱癌发生中的表达、功能和潜在机制尚未完全阐明。在本研究中,我们的数据表明 ZFAS1 在膀胱癌组织和细胞系中的表达显著上调。此外,Kaplan-Meier 分析显示,ZFAS1 高表达与膀胱癌患者不良无进展生存期(PFS)(P=0.0034<0.01)和总生存期(OS)(P=0.0041<0.01)显著相关。此外,沉默 ZFAS1 的表达可以显著抑制膀胱癌细胞的增殖和集落形成,阻滞细胞周期,促进细胞凋亡,抑制细胞迁移。此外,生物信息学分析、荧光素酶报告基因检测和下拉实验显示 ZFAS1 可直接与 miR-329 相互作用。最后,挽救实验证实 miR-329 抑制剂逆转了 ZFAS1 敲低对膀胱癌细胞的肿瘤抑制作用。综上所述,我们的研究结果表明 ZFAS1 可以作为膀胱癌发生的癌基因,并发现了 ZFAS1 海绵 miR-329 的功能调节网络。