Predictive value of pseudouridine in prostate cancer.
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BACKGROUND: Recent studies have shown that certain small nucleolar RNAs (H/ACA snoRNAs) and the protein dyskerin (DKC1) are upregulated in prostate cancer and are thought to contribute to progression of disease. These components convert uridine to pseudouridine (abbreviated ), a type of post-transcriptional modification of RNA. Given the increased abundance of H/ACA snoRNAs and expression of DKC1 in prostate carcinomas, and because whole-body turnover of RNA increases in support of rapidly-growing cancer cells, we examined the value of pseudouridine as a biomarker for prostate cancer. METHODS: Using a monoclonal antibody against pseudouridine, we tested its ability to distinguish between two 25-base RNA oligonucleotide sequences that differed by only one -substitution, and subsequently measured in RNA isolated from several prostate cancer cell lines representing different stages of disease using dot blot assays and pseudouridinylated RNA linked immunosorbent assay (PURLISA). We also performed immunohistochemistry on a tissue micro array (12 cases/24 cores) containing prostate adenocarcinomas and normal adjacent tissue (NAT). RESULTS: High levels of pseudouridine were detected in androgen-independent cell lines (PC3 and Du145) compared to androgen-sensitive (LNCaP) and immortalized human prostate (RWPE) cells. Immunohistochemistry of a tissue micro array (TMA) containing normal adjacent and cancerous prostate tissue revealed a significant difference in immunoreactivity between normal and malignant tissue (P 0.0001). CONCLUSION: Our results provide new information on the relationship between pseudouridine expression and clinical progression of prostate cancer.
