Articles written in Journal of Biosciences
Volume 44 Issue 4 September 2019 Article ID 0102 Review
Prostate cancer (PCa) represents the most frequently diagnosed cancer in men. Cisplatin, also known as cis-diamminedichloroplatinum(DDP), is a standard chemotherapeutic agent used to treat PCa, and DDP resistance remains one important obstacle inDDP-based chemotherapy. In our research, we found miR-425-5p was down-regulated in PCa and even lower in DDP-resistantPCa determined by quantitative polymerase chain reaction; in contrast, GSK3b mRNA expression was upregulated in PCa andeven higher in DDP-resistant PCa. Moreover, there was a modest but significant inverse correlation between the expression ofGSK3bmRNA and miR-425-5p. Functional experiments showed that miR-425-5p mimic inhibited DDP resistance as evidencedby a promoted apoptosis rate (flow cytometry) and suppressed cell viability (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay) and expressions of MDR1 andMRP1 (western blotting) in DU145/DDP and PC3/DDP cells. Luciferase reporterassay and RNA immunoprecipitation identifiedGSK3b was a potential target of miR-425-5p. The effect ofmiR-425-5pmimic onDDP resistance was partially reversed by pcDNA-GSK3b. Mechanically, miR-425-5p mimic reduced expression of b-catenin,cyclin D1 and C-myc, which was further blocked when GSK3b overexpressed. In vivo experiments, recovery of GSK3bprevented xenograft tumor growth and DDP resistance in the presence of miR-425-5p mimic. To sum up, miR-425-5p upregulationmight sensitize human PCa to DDP by targeting GSK3b and inactivating the Wnt/b-catenin signaling pathway.
Volume 45, 2020
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