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Cancer Epidemiol Biomarkers Prev. 2015 Jan;24(1):268-75. doi: 10.1158/1055-9965.EPI-14-0377. Epub 2014 Nov 12.

Identification and diagnostic performance of a small RNA within the PCA3 and BMCC1 gene locus that potentially targets mRNA.

Author information

1
Academic Urology Unit and Academic Unit of Molecular Oncology, University of Sheffield, Sheffield, United Kingdom.
2
Department of Urology, University of Queensland, Brisbane, Australia.
3
Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee. Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee.
4
Department of Pathology, University of Erlangen, Erlangen, Germany.
5
Department of Urology, Josephine Nefkens Institute, Erasmus MC, Rotterdam, the Netherlands.
6
Nuffield Department of Surgery, University of Oxford, Oxford, United Kingdom.
7
Academic Urology Unit and Academic Unit of Molecular Oncology, University of Sheffield, Sheffield, United Kingdom. j.catto@sheffield.ac.uk.

Abstract

BACKGROUND:

PCA3 is a long noncoding RNA (lncRNA) with unknown function, upregulated in prostate cancer. LncRNAs may be processed into smaller active species. We hypothesized this for PCA3.

METHODS:

We computed feasible RNA hairpins within the BMCC1 gene (encompassing PCA3) and searched a prostate transcriptome for these. We measured expression using qRT-PCR in three cohorts of prostate cancer tissues (n = 60), exfoliated urinary cells (n = 484 with cancer and n = 166 controls), and in cell lines (n = 22). We used in silico predictions and RNA knockup to identify potential mRNA targets of short transcribed RNAs.

RESULTS:

We predicted 13 hairpins, of which PCA3-shRNA2 was most abundant within the prostate transcriptome. PCA3-shRNA2 is located within intron 1 of PCA3 and appears regulated by androgens. Expression of PCA3-shRNA2 was upregulated in malignant prostatic tissues, exfoliated urinary cells from men with prostate cancer (13-273 fold change; t test P < 0.003), and closely correlated to PCA3 expression (r = 0.84-0.93; P < 0.001). Urinary PCA3-shRNA2 (C-index, 0.75-0.81) and PCA3 (C-index, 0.78) could predict the presence of cancer in most men. PCA3-shRNA2 knockup altered the expression of predicted target mRNAs, including COPS2, SOX11, WDR48, TEAD1, and Noggin. PCA3-shRNA2 expression was negatively correlated with COPS2 in patient samples (r = -0.32; P < 0.001).

CONCLUSION:

We identified a short RNA within PCA3, whose expression is correlated to PCA3, which may target mRNAs implicated in prostate biology.

IMPACT:

This short RNA is stable ex vivo, suggesting a role as a robust biomarker. We identify cytoplasmic enrichment of this RNA and potential targeting of mRNAs implicated in prostate carcinogenesis.

PMID:
25392181
DOI:
10.1158/1055-9965.EPI-14-0377
[Indexed for MEDLINE]
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