Liu Bei-Bei, Ma Tao, Sun Wei, Gao Wu-Yue, Liu Jian-Min, Li Li-Qiang, Li Wen-Yong, Wang Sheng, Guo Yuan-Yuan
Department of Urology, the First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233000, China.
Korean J Physiol Pharmacol. 2021 Mar 1;25(2):119-129. doi: 10.4196/kjpp.2021.25.2.119.
Bladder cancer is one of the most common types of cancer. Most gene mutations related to bladder cancer are dominantly acquired gene mutations and are not inherited. Previous comparative transcriptome analysis of urinary bladder cancer and control samples has revealed a set of genes that may play a role in tumor progression. Here we set out to investigate further the expression of two candidate genes, centromere protein U (CENPU) and mitochondrial ribosomal protein s28 (MRPS28) to better understand their role in bladder cancer pathogenesis. Our results confirmed that CENPU is up-regulated in human bladder cancer tissues at mRNA and protein levels. Gain-of-function and loss-of-function studies in T24 human urinary bladder cancer cell line revealed a hierarchical relationship between CENPU and MRPS28 in the regulation of cell viability, migration and invasion activity. CENPU expression was also up-regulated in nude mice xenograft model of bladder cancer and mice overexpressing CENPU had significantly higher tumor volume. In summary, our findings identify CENPU and MRPS28 in the molecular pathogenesis of bladder cancer and suggest that CENPU enhances the progression of bladder cancer by promoting MRPS28 expression.
膀胱癌是最常见的癌症类型之一。大多数与膀胱癌相关的基因突变是显性获得性基因突变，而非遗传性突变。先前对膀胱癌和对照样本进行的比较转录组分析已经揭示了一组可能在肿瘤进展中起作用的基因。在此，我们着手进一步研究两个候选基因，着丝粒蛋白U（CENPU）和线粒体核糖体蛋白s28（MRPS28）的表达情况，以更好地了解它们在膀胱癌发病机制中的作用。我们的结果证实，CENPU在人膀胱癌组织中的mRNA和蛋白质水平均上调。在T24人膀胱癌细胞系中进行的功能获得和功能丧失研究揭示了CENPU和MRPS28在调节细胞活力、迁移和侵袭活性方面的层级关系。在膀胱癌裸鼠异种移植模型中，CENPU表达也上调，并且过表达CENPU的小鼠肿瘤体积显著更大。总之，我们的研究结果确定了CENPU和MRPS28在膀胱癌分子发病机制中的作用，并表明CENPU通过促进MRPS28表达增强膀胱癌的进展。
