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 in DDP-based chemotherapy. In our research, we found miR-425-5p was down-regulated in PCa and even lower in DDP-resistant PCa determined by quantitative polymerase chain reaction; in contrast, GSK3β mRNA expression was upregulated in PCa and even higher in DDP-resistant PCa. Moreover, there was a modest but significant inverse correlation between the expression of GSK3β mRNA and miR-425-5p. Functional experiments showed that miR-425-5p mimic inhibited DDP resistance as evidenced by a promoted apoptosis rate (flow cytometry) and suppressed cell viability (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay) and expressions of MDR1 andMRP1 (western blotting) in DU145/DDP and PC3/DDP cells. Luciferase reporter assay and RNA immunoprecipitation identifiedGSK3β was a potential target of miR-425-5p. The effect ofmiR-425-5pmimic on DDP resistance was partially reversed by pcDNA-GSK3β. Mechanically, miR-425-5p mimic reduced expression of β- catenin, cyclin D1 and C-myc, which was further blocked when GSK3β overexpressed. In vivo experiments, recovery of GSK3β prevented xenograft tumor growth and DDP resistance in the presence of miR-425-5p mimic. To sum up, miR-425-5p upregulation might sensitize human PCa to DDP by targeting GSK3β and inactivating the Wnt/β- catenin signaling pathway.
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Authors | Sheng Liu, Qin Wang, Yin Liu, Zong-Yu Xia |
Journal | Journal of biosciences
(J Biosci)
Vol. 44
Issue 4
(Sep 2019)
ISSN: 0973-7138 [Electronic] India |
PMID | 31502580
(Publication Type: Journal Article)
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Chemical References |
- CTNNB1 protein, human
- MIRN425 microRNA, human
- MicroRNAs
- beta Catenin
- Glycogen Synthase Kinase 3 beta
- Cisplatin
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Topics |
- Animals
- Apoptosis
(drug effects)
- Carcinogenesis
(genetics)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Cisplatin
(pharmacology)
- Drug Resistance, Neoplasm
- Gene Expression Regulation, Neoplastic
(drug effects)
- Glycogen Synthase Kinase 3 beta
(genetics)
- Humans
- Male
- Mice
- MicroRNAs
(genetics)
- Prostatic Neoplasms
(drug therapy, genetics, pathology)
- Wnt Signaling Pathway
(drug effects)
- Xenograft Model Antitumor Assays
- beta Catenin
(genetics)
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