Department of Urology, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Zhejiang, 310014, China.
Department of Urology, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Zhejiang, 310014, China.
Biomed Pharmacother. 2018 Dec;108:1039-1047. doi: 10.1016/j.biopha.2018.09.100. Epub 2018 Sep 28.
MicroRNAs (miRNAs) have been widely studied in various human cancers, including bladder cancer. Previous report revealed that miR-125a-5p is downregulated in urothelial carcinomas. However, the biological function and molecular mechanism of miR-125a-5p in bladder cancer has not been elucidated. Therefore, this study focused on the role of miR-125a-5p in bladder cancer. The expression levels of miR-125a-5p were firstly tested in one normal cell line and four bladder cancer cell lines with qRT-PCR. The relative lower expression of miR-125a-5p was detected in bladder cancer cells. To confirm the effects of ectopic expression of miR-125a-5p on the biological behaviors of bladder cancer cells, gain-of-function assays were carried out. According to experimental results, miR-125a-5p overexpression suppressed cell proliferation and cell cycle progression, induced cell apoptosis. Moreover, overexpression of miR-125a-5p suppressed cell migration and invasion and reversed epithelial-mesenchymal transition (EMT). Mechanism investigation indicated that FUT4 is a target mRNA of miR-125a-5p in bladder cancer. The effects of FUT4 on cell proliferation, apoptosis, migration and invasion were identified by conducting gain-of-function assays. Finally, rescue assays indicated that FUT4 can reverse the effects of miR-125a-5p on bladder cancer progression. In summary, miR-125a-5p suppresses bladder cancer progression through targeting FUT4.
微小 RNA(miRNAs)在各种人类癌症中都得到了广泛的研究,包括膀胱癌。之前的报告表明 miR-125a-5p 在尿路上皮癌中下调。然而,miR-125a-5p 在膀胱癌中的生物学功能和分子机制尚未阐明。因此,本研究集中于 miR-125a-5p 在膀胱癌中的作用。首先通过 qRT-PCR 在一个正常细胞系和四个膀胱癌细胞系中检测 miR-125a-5p 的表达水平。在膀胱癌细胞中检测到 miR-125a-5p 的相对较低表达。为了证实异位表达 miR-125a-5p 对膀胱癌细胞生物学行为的影响,进行了功能获得性实验。根据实验结果,miR-125a-5p 的过表达抑制细胞增殖和细胞周期进程,诱导细胞凋亡。此外,过表达 miR-125a-5p 抑制细胞迁移和侵袭,并逆转上皮-间充质转化(EMT)。机制研究表明,FUT4 是膀胱癌中 miR-125a-5p 的靶 mRNA。通过进行功能获得性实验鉴定了 FUT4 对细胞增殖、凋亡、迁移和侵袭的影响。最后,挽救实验表明 FUT4 可以逆转 miR-125a-5p 对膀胱癌进展的影响。总之,miR-125a-5p 通过靶向 FUT4 抑制膀胱癌的进展。