Long Qian, An Xin, Chen Miao, Wang Nan, Sui Silei, Li Yixin, Zhang Changlin, Lee Kaping, Wang Xiaonan, Tian Tian, Pan Yangxun, Qiu Huijuan, Xie Fangyun, Deng Wuguo, Zheng Fufu, He Liru
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
College of Life Science, Jiaying University, Meizhou, China.
Front Oncol. 2020 Oct 7;10:568015. doi: 10.3389/fonc.2020.568015. eCollection 2020.
Abnormal expression or mutation of RNA splicing proteins are widely observed in human cancers. Here, we identified poly(U) binding splicing factor 60 () as one of the most differentially expressed genes out of 97 RNA splicing proteins between normal and bladder cancer tissues by bioinformatics analysis of TCGA bladder cancer expression data. The expression of was significantly higher in tumor tissues, while high expression was associated with malignant phenotypes of bladder cancer and shorter survival time. Moreover, we identified aurora kinase A () as a new downstream target of in bladder cancer cells. knockdown significantly inhibited cell viability and colony formation capacity in bladder cancer cells, whereas overexpression reversed this inhibition effect. Overexpression of significantly promoted cell viability and colony formation in bladder cancer cells, while treatment with specific inhibitor reversed this promotive effect. Mechanistically, specifically bound to the promoter, thereby activating its transcription and expression. Furthermore, we showed that there was a significant positive correlation between and expression in bladder cancer tissues, and and expression contributed to tumor progression and malignant phenotypes in the patients with bladder cancer. Collectively, these results indicate that the axis plays a key role in regulating tumorigenesis and progression of bladder cancer, and may be a potential prognostic biomarker and therapeutic target for bladder cancer patients.
RNA剪接蛋白的异常表达或突变在人类癌症中广泛存在。在此,我们通过对TCGA膀胱癌表达数据进行生物信息学分析,从97种RNA剪接蛋白中确定聚(U)结合剪接因子60()是正常组织与膀胱癌组织之间差异表达最为显著的基因之一。在肿瘤组织中的表达显著更高,而高表达与膀胱癌的恶性表型及较短生存期相关。此外,我们确定极光激酶A()是膀胱癌细胞中 的一个新的下游靶点。敲低 可显著抑制膀胱癌细胞的细胞活力和集落形成能力,而过表达 则可逆转这种抑制作用。 的过表达显著促进膀胱癌细胞的细胞活力和集落形成,而用 特异性抑制剂处理可逆转这种促进作用。机制上, 特异性结合至 启动子,从而激活其转录和表达。此外,我们发现膀胱癌组织中 和 的表达之间存在显著正相关,且 和 的表达促进膀胱癌患者的肿瘤进展和恶性表型。总体而言,这些结果表明 轴在调节膀胱癌的发生和进展中起关键作用,可能是膀胱癌患者潜在的预后生物标志物和治疗靶点。