Regulation of Expression of Deoxyhypusine Hydroxylase (DOHH), the Enzyme That Catalyzes the Activation of eIF5A, by miR-331-3p and miR-642-5p in Prostate Cancer Cells
Copyright policy )Regulation of Expression of Deoxyhypusine Hydroxylase (DOHH), the Enzyme That Catalyzes the Activation of eIF5A, by miR-331-3p and miR-642-5p in Prostate Cancer Cells
The enzyme deoxyhypusine hydroxylase (DOHH) catalyzes the activation of eukaryotic translation initiation factor (eIF5A), a protein essential for cell growth. Using bioinformatic predictions and reporter gene assays, we have identified a 182-nt element within the DOHH 3'-untranslated region (3'-UTR) that contains a number of target sites for miR-331-3p and miR-642-5p. Quantitative RT-PCR studies demonstrated overexpression of DOHH mRNA and underexpression of miR-331-3p and miR-642-5p in several prostate cancer cell lines compared with normal prostate epithelial cells. Transient overexpression of miR-331-3p and/or miR-642-5p in DU145 prostate cancer cells reduced DOHH mRNA and protein expression and inhibited cell proliferation. We observed synergistic growth inhibition with the combination of miR-331-3p and miR-642-5p and mimosine, a pharmacological DOHH inhibitor. Finally, we identified a significant inverse relationship between the expression of miR-331-3p or miR-642-5p and DOHH in a cohort of human prostate cancer tissues. Our results suggest a novel role for miR-331-3p and miR-642-5p in the control of prostate cancer cell growth via the regulation of DOHH expression and eIF5A activity.
- Harry Perkins Institute of Medical Research Australia
- Royal Perth Hospital Australia
- University of Western Australia Australia
Male, Prostatic Neoplasms, RNA-Binding Proteins, Eukaryotic Translation Initiation Factor 5A, Middle Aged, Gene Expression Regulation, Enzymologic, Mixed Function Oxygenases, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, MicroRNAs, Peptide Initiation Factors, Cell Line, Tumor, Humans, RNA, Neoplasm, 3' Untranslated Regions, Aged
Male, Prostatic Neoplasms, RNA-Binding Proteins, Eukaryotic Translation Initiation Factor 5A, Middle Aged, Gene Expression Regulation, Enzymologic, Mixed Function Oxygenases, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, MicroRNAs, Peptide Initiation Factors, Cell Line, Tumor, Humans, RNA, Neoplasm, 3' Untranslated Regions, Aged
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).49 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!