Drayton, R.M., Rehman, I., Clarke, R. et al. (13 more authors) (2015) Identification and Diagnostic Performance of a Small RNA within the PCA3 and BMCC1 Gene Locus That Potentially Targets mRNA. Cancer Epidemiology, Biomarkers and Prevention, 24 (1). 268 - 275. ISSN 1055-9965
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2014 American Association for Cancer Research. This is an author produced version of a paper subsequently published in Cancer Epidemiology, Biomarkers and Prevention. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 13 Oct 2015 15:40 |
Last Modified: | 22 Mar 2018 15:23 |
Published Version: | http://dx.doi.org/10.1158/1055-9965.EPI-14-0377 |
Status: | Published |
Publisher: | American Association for Cancer Research |
Refereed: | Yes |
Identification Number: | 10.1158/1055-9965.EPI-14-0377 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:90830 |