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MiR-187 Targets the Androgen-Regulated Gene ALDH1A3 in Prostate Cancer.

Casanova-Salas I, Masiá E, Armiñán A, Calatrava A, Mancarella C, Rubio-Briones J, Scotlandi K, Vicent MJ, López-Guerrero JA - PLoS ONE (2015)

Bottom Line: Supporting these data, the expression of ALDH1A3 was found significantly (p<0.0001) up-regulated in PCa samples and inversely correlated (p<0.0001) with miR-187 expression, its expression being directly associated with Gleason score (p = 0.05).The expression of ALDH1A3 was measured in urine samples to evaluate the predictive capability of this biomarker for the presence of PCa and, at a signification level of 10%, PSA and also ALDH1A3 were significantly associated with a positive biopsy of PCa.In conclusion, our data illustrate for the first time the role of ALDH1A3 as a miR-187 target in PCa and provide insights in the utility of using this protein as a new biomarker for PCa.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, Valencia, Spain.

ABSTRACT
miRNAs are predicted to control the activity of approximately 60% of all protein-coding genes participating in the regulation of several cellular processes and diseases, including cancer. Recently, we have demonstrated that miR-187 is significantly downregulated in prostate cancer (PCa) and here we propose a proteomic approach to identify its potential targets. For this purpose, PC-3 cells were transiently transfected with miR-187 precursor and miRNA mimic negative control. Proteins were analyzed by a two-dimensional difference gel electrophoresis (2D-DIGE) and defined as differentially regulated if the observed fold change was ±1.06. Then, MALDI-TOF MS analysis was performed after protein digestion and low abundance proteins were identified by LC-MS/MS. Peptides were identified by searching against the Expasy SWISS PROT database, and target validation was performed both in vitro by western blot and qRT-PCR and in clinical samples by qRT-PCR, immunohistochemistry and ELISA. DIGE analysis showed 9 differentially expressed spots (p<0.05) and 7 showed a down-regulated expression upon miR-187 re-introduction. Among these targets we identified aldehyde dehydrogenase 1A3 (ALDH1A3). ALDH1A3 expression was significantly downregulated in PC3, LNCaP and DU-145 cells after miR-187 re-introduction. Supporting these data, the expression of ALDH1A3 was found significantly (p<0.0001) up-regulated in PCa samples and inversely correlated (p<0.0001) with miR-187 expression, its expression being directly associated with Gleason score (p = 0.05). The expression of ALDH1A3 was measured in urine samples to evaluate the predictive capability of this biomarker for the presence of PCa and, at a signification level of 10%, PSA and also ALDH1A3 were significantly associated with a positive biopsy of PCa. In conclusion, our data illustrate for the first time the role of ALDH1A3 as a miR-187 target in PCa and provide insights in the utility of using this protein as a new biomarker for PCa.

No MeSH data available.


Related in: MedlinePlus

Diagnostic role of ALDH1A3 in urine samples.ROC curves from PSA and ALDH1A3 for predicting PCa in urine samples. The areas under the curve are 0.610 (95%CI 0.509–0.710; p = 0.036 and 0.591 (95% CI 0.490–0.692; p = 0.083) respectively. At a significance level of 10%, both PSA and ALDH1A3 were significantly associated with a positive biopsy of PCa.
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pone.0125576.g005: Diagnostic role of ALDH1A3 in urine samples.ROC curves from PSA and ALDH1A3 for predicting PCa in urine samples. The areas under the curve are 0.610 (95%CI 0.509–0.710; p = 0.036 and 0.591 (95% CI 0.490–0.692; p = 0.083) respectively. At a significance level of 10%, both PSA and ALDH1A3 were significantly associated with a positive biopsy of PCa.

Mentions: To further explore the role of ALDH1A3 in the diagnostic setting we performed an ELISA assay to measure ALDH1A3 expression in urine (n = 123). A univariate logistic regression model was performed to evaluate the predictive capability of this biomarker, together with PSA, for the presence of PCa in diagnostic biopsies. At a significance level of 10%, PSA and ALDH1A3 were both significantly associated with a positive biopsy of PCa (Fig 5).


MiR-187 Targets the Androgen-Regulated Gene ALDH1A3 in Prostate Cancer.

Casanova-Salas I, Masiá E, Armiñán A, Calatrava A, Mancarella C, Rubio-Briones J, Scotlandi K, Vicent MJ, López-Guerrero JA - PLoS ONE (2015)

Diagnostic role of ALDH1A3 in urine samples.ROC curves from PSA and ALDH1A3 for predicting PCa in urine samples. The areas under the curve are 0.610 (95%CI 0.509–0.710; p = 0.036 and 0.591 (95% CI 0.490–0.692; p = 0.083) respectively. At a significance level of 10%, both PSA and ALDH1A3 were significantly associated with a positive biopsy of PCa.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4430273&req=5

pone.0125576.g005: Diagnostic role of ALDH1A3 in urine samples.ROC curves from PSA and ALDH1A3 for predicting PCa in urine samples. The areas under the curve are 0.610 (95%CI 0.509–0.710; p = 0.036 and 0.591 (95% CI 0.490–0.692; p = 0.083) respectively. At a significance level of 10%, both PSA and ALDH1A3 were significantly associated with a positive biopsy of PCa.
Mentions: To further explore the role of ALDH1A3 in the diagnostic setting we performed an ELISA assay to measure ALDH1A3 expression in urine (n = 123). A univariate logistic regression model was performed to evaluate the predictive capability of this biomarker, together with PSA, for the presence of PCa in diagnostic biopsies. At a significance level of 10%, PSA and ALDH1A3 were both significantly associated with a positive biopsy of PCa (Fig 5).

Bottom Line: Supporting these data, the expression of ALDH1A3 was found significantly (p<0.0001) up-regulated in PCa samples and inversely correlated (p<0.0001) with miR-187 expression, its expression being directly associated with Gleason score (p = 0.05).The expression of ALDH1A3 was measured in urine samples to evaluate the predictive capability of this biomarker for the presence of PCa and, at a signification level of 10%, PSA and also ALDH1A3 were significantly associated with a positive biopsy of PCa.In conclusion, our data illustrate for the first time the role of ALDH1A3 as a miR-187 target in PCa and provide insights in the utility of using this protein as a new biomarker for PCa.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, Valencia, Spain.

ABSTRACT
miRNAs are predicted to control the activity of approximately 60% of all protein-coding genes participating in the regulation of several cellular processes and diseases, including cancer. Recently, we have demonstrated that miR-187 is significantly downregulated in prostate cancer (PCa) and here we propose a proteomic approach to identify its potential targets. For this purpose, PC-3 cells were transiently transfected with miR-187 precursor and miRNA mimic negative control. Proteins were analyzed by a two-dimensional difference gel electrophoresis (2D-DIGE) and defined as differentially regulated if the observed fold change was ±1.06. Then, MALDI-TOF MS analysis was performed after protein digestion and low abundance proteins were identified by LC-MS/MS. Peptides were identified by searching against the Expasy SWISS PROT database, and target validation was performed both in vitro by western blot and qRT-PCR and in clinical samples by qRT-PCR, immunohistochemistry and ELISA. DIGE analysis showed 9 differentially expressed spots (p<0.05) and 7 showed a down-regulated expression upon miR-187 re-introduction. Among these targets we identified aldehyde dehydrogenase 1A3 (ALDH1A3). ALDH1A3 expression was significantly downregulated in PC3, LNCaP and DU-145 cells after miR-187 re-introduction. Supporting these data, the expression of ALDH1A3 was found significantly (p<0.0001) up-regulated in PCa samples and inversely correlated (p<0.0001) with miR-187 expression, its expression being directly associated with Gleason score (p = 0.05). The expression of ALDH1A3 was measured in urine samples to evaluate the predictive capability of this biomarker for the presence of PCa and, at a signification level of 10%, PSA and also ALDH1A3 were significantly associated with a positive biopsy of PCa. In conclusion, our data illustrate for the first time the role of ALDH1A3 as a miR-187 target in PCa and provide insights in the utility of using this protein as a new biomarker for PCa.

No MeSH data available.


Related in: MedlinePlus