TY - JOUR
T1 - Identification and Diagnostic Performance of a Small RNA within the PCA3 and BMCC1 Gene Locus That Potentially Targets mRNA
AU - Drayton, RM
AU - Rehman, I
AU - Clarke, R
AU - Zhao, ZM
AU - Pang, K
AU - Miah, S
AU - Stoehr, R
AU - Hartmann, A
AU - Blizard, S
AU - Lavin, M
AU - Bryant, HE
AU - Martens, Elena
AU - Jenster, Guido
AU - Hamdy, FC
AU - Gardiner, RA
AU - Catto, JWF
PY - 2015
Y1 - 2015
N2 - 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. Weidentify cytoplasmic enrichment of this RNA and potential targeting of mRNAs implicated in prostate carcinogenesis. (C) 2014 AACR.
AB - 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. Weidentify cytoplasmic enrichment of this RNA and potential targeting of mRNAs implicated in prostate carcinogenesis. (C) 2014 AACR.
U2 - 10.1158/1055-9965.EPI-14-0377
DO - 10.1158/1055-9965.EPI-14-0377
M3 - Article
SN - 1055-9965
VL - 24
SP - 268
EP - 275
JO - Cancer Epidemiology Biomarkers & Prevention
JF - Cancer Epidemiology Biomarkers & Prevention
IS - 1
ER -