Role of miR-125a-5p Clarified in Bladder Cancer

Researchers found miR-125a-5p inhibits bladder cancer progression by targeting FUT4, an oncogene.¹ Previous studies have shown miR-125a-5p is downregulated in urothelial cancers, but until now, the mechanism of miR-125a-5p in bladder cancer has not been demonstrated. The study results were published in Biomedicine & Pharmacotherapy.

A series of experiments were conducted to elucidate the biological mechanism of miR-125a-5p in bladder cancer. In 4 bladder cancer cell lines, miR-125a-5p was shown to have lower expression levels relative to 1 normal cell line. When miR-125a-5p was overexpressed in gain-of-function assays, cell proliferation was suppressed, cell-cycle progress was halted, and apoptosis was induced. Overexpression of miR-125a-5p was also found to block cell migration and invasion as well as reverse epithelial-mesenchymal transition. Altogether, the findings indicate miR-125a-5p acts as an inhibitor in bladder cancer progression.

Next, the researcher sought to identify the downstream mRNA target of miR-125a-5p. Bioinformatics tools identified 4 candidate mRNA targets. Luciferase reporter assay narrowed the search, showing binding between miR-125a-5p and only 1 candidate mRNA target, FUT4. As expected, gain-of-function assays revealed that FUT4 behaved like an oncogene, promoting cell proliferation and cell-cycle progression while blocking cell apoptosis.

Rescue assays were performed to confirm that FUT4 and miR-125a-5p interact in order to regulate bladder cancer progression. The assays provided validation, showing that FUT4 participates in miR-125a-5p–mediated bladder cancer progression.

“In conclusion, miR-125a-5p acts as a tumor inhibitor in bladder cancer via targeting FUT4,” the study authors wrote. “Our findings may contribute to finding a novel molecular pathway in bladder cancer.”

Reference

1. Zhang Y, Zhang D, Lv J, Wang S, and Zhang Q. MiR-125a-5p suppresses bladder cancer progression through targeting FUT4[accepted September 18, 2018]. Biomed Pharmacother. 2018;108:1039-1047. doi: 10.1016/j.biopha.2018.09.100