Predictive value of pseudouridine in prostate cancer.

ABSTRACT:

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.

SUBMITTER: Stockert JA 

PROVIDER: S-EPMC6734038 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature