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miR-125a-5p 通过靶向 FUT4 抑制膀胱癌进展。

MiR-125a-5p suppresses bladder cancer progression through targeting FUT4.

机构信息

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.

出版信息

Biomed Pharmacother. 2018 Dec;108:1039-1047. doi: 10.1016/j.biopha.2018.09.100. Epub 2018 Sep 28.

Abstract

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.

摘要

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。

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