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.
Written by:
Epis MR, Giles KM, Kalinowski FC, Barker A, Cohen RJ, Leedman PJ. Are you the author?
Laboratory for Cancer Medicine, Western Australian Institute for Medical Research and University of Western Australia Centre for Medical Research, Royal Perth Hospital, Perth, Western Australia 6000, Australia.
Reference: J Biol Chem. 2012 Oct 12;287(42):35251-9.
doi: 10.1074/jbc.M112.374686
PubMed Abstract
PMID: 22908221
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