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

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.

Keywords: Bladder cancer; FUT4; MiR-125a-5p; Migration; Proliferation.

MeSH terms

  • Apoptosis / genetics
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Down-Regulation / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Fucosyltransferases / genetics*
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Lewis X Antigen / genetics*
  • MicroRNAs / genetics*
  • RNA, Messenger / genetics
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology*

Substances

  • Lewis X Antigen
  • MIRN125 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • FUT4 protein, human
  • Fucosyltransferases