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.

Abstract

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.

• Authors: Michael R Epis, Keith M Giles, Felicity C Kalinowski, Andrew Barker, Ronald J Cohen, Peter J Leedman
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 287 Issue 42 Pg. 35251-35259 (Oct 12 2012) ISSN: 1083-351X [Electronic] United States
• PMID: 22908221 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 3' Untranslated Regions
• MIRN331 microRNA, human
• MIRN642 microRNA, human
• MicroRNAs
• Neoplasm Proteins
• Peptide Initiation Factors
• RNA, Neoplasm
• RNA-Binding Proteins
• eukaryotic translation initiation factor 5A
• Mixed Function Oxygenases
• deoxyhypusine hydroxylase

Topics

• 3' Untranslated Regions (genetics)
• Aged
• Cell Line, Tumor
• Gene Expression Regulation, Enzymologic
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• MicroRNAs (genetics, metabolism)
• Middle Aged
• Mixed Function Oxygenases (biosynthesis, genetics)
• Neoplasm Proteins (genetics, metabolism)
• Peptide Initiation Factors (genetics, metabolism)
• Prostatic Neoplasms (genetics, metabolism, pathology)
• RNA, Neoplasm (genetics, metabolism)
• RNA-Binding Proteins (genetics, metabolism)