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

TitleIdentification and diagnostic performance of a small RNA within the PCA3 and BMCC1 gene locus that potentially targets mRNA
Authors
Issue Date2015
Citation
Cancer Epidemiology Biomarkers and Prevention, 2015, v. 24, n. 1, p. 268-275 How to Cite?
AbstractBackground: 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 qRTPCR 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.Weidentify cytoplasmic enrichment of thisRNA and potential targeting of mRNAs implicated in prostate carcinogenesis.
Persistent Identifierhttp://hdl.handle.net/10722/328721
ISSN
2023 Impact Factor: 3.7
2023 SCImago Journal Rankings: 1.688
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorDrayton, Ross M.-
dc.contributor.authorRehman, Ishtiaq-
dc.contributor.authorClarke, Raymond-
dc.contributor.authorZhao, Zhongming-
dc.contributor.authorPang, Karl-
dc.contributor.authorMiah, Saiful-
dc.contributor.authorStoehr, Robert-
dc.contributor.authorHartmann, Arndt-
dc.contributor.authorBlizard, Sheila-
dc.contributor.authorLavin, Martin-
dc.contributor.authorBryant, Helen E.-
dc.contributor.authorMartens-Uzunova, Elena S.-
dc.contributor.authorJenster, Guido-
dc.contributor.authorHamdy, Freddie C.-
dc.contributor.authorGardiner, Robert A.-
dc.contributor.authorCatto, James W.F.-
dc.date.accessioned2023-07-22T06:23:24Z-
dc.date.available2023-07-22T06:23:24Z-
dc.date.issued2015-
dc.identifier.citationCancer Epidemiology Biomarkers and Prevention, 2015, v. 24, n. 1, p. 268-275-
dc.identifier.issn1055-9965-
dc.identifier.urihttp://hdl.handle.net/10722/328721-
dc.description.abstractBackground: 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 qRTPCR 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.Weidentify cytoplasmic enrichment of thisRNA and potential targeting of mRNAs implicated in prostate carcinogenesis.-
dc.languageeng-
dc.relation.ispartofCancer Epidemiology Biomarkers and Prevention-
dc.titleIdentification and diagnostic performance of a small RNA within the PCA3 and BMCC1 gene locus that potentially targets mRNA-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1158/1055-9965.EPI-14-0377-
dc.identifier.pmid25392181-
dc.identifier.scopuseid_2-s2.0-84921059049-
dc.identifier.volume24-
dc.identifier.issue1-
dc.identifier.spage268-
dc.identifier.epage275-
dc.identifier.isiWOS:000348030700032-

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