• miR-425-5p suppresses tumorigenesis and DDP resistance in human-prostate cancer by targeting GSK3 β and inactivating the Wnt/β-catenin signaling pathway

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    • Keywords

       

      & beta; -Catenin; DDP resistance; GSK3& beta; ; miR-425-5p; prostate cancer (PCa)

    • Abstract

       

      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.

    • Author Affiliations

       

      SHENG LIU1 QIN WANG2 YIN LIU1 ZONG-YU XIA1

      1. Department of Urology, Chongqing Three Gorges Central Hospital, Chongqing, People’s Republic of China
      2. Department of Oncology, Chongqing Three Gorges Central Hospital, Chongqing, People’s Republic of China
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  • Journal of Biosciences | News

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