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Updated: Jul 30, 2025
miRNA Expression Analyses in Prostate Cancer Clinical Tissues
Published on: September 8, 2015
Investigating microRNA Profiles in Prostate Cancer Bone Metastases and Functional Effects of microRNA-23c and
Helena Järemo1, Julius Semenas1, Sofia Halin Bergström1
1Department of Medical Biosciences, Pathology, Umeå University, 901 87 Umeå, Sweden.
Abstract:
MicroRNAs (miRNAs) are aberrantly expressed in prostate cancer (PC), but comprehensive knowledge about their levels and function in metastatic PC is lacking. Here, we explored the differential expression of miRNA profiles during PC progression to bone metastasis, and further focused on the downregulation of miRNA-23c and -4328 and their impact on PC growth in experimental models. Using microarray screening, the levels of 1510 miRNAs were compared between bone metastases (n = 14), localized PC (n = 7) and benign prostate tissue (n = 7). Differentially expressed miRNAs (n = 4 increased and n = 75 decreased, p < 0.05) were identified, of which miRNA-1, -23c, -143-3p, -143-5p, -145-3p, -205-5p, -221-3p, -222-3p and -4328 showed consistent downregulation during disease progression (benign > localized PC > bone metastases). The downregulation of miRNA-23c and -4328 was confirmed by reverse transcription and quantitative polymerase chain reaction analysis of 67 metastasis, 12 localized PC and 12 benign prostate tissue samples. The stable overexpression of miRNA-23c and -4328 in the 22Rv1 and PC-3 cell lines resulted in reduced PC cell growth in vitro, and in the secretion of high levels of miRNA-23c (but not -4328) in extracellular vesicles. However, no tumor suppressive effects were observed from miRNA-23c overexpression in PC-3 cells subcutaneously grown in mice. In conclusion, bone metastases display a profound reduction of miRNA levels compared to localized PC and benign disease. The downregulation of those miRNAs, including miRNA-23c and -4328, may lead to a loss of tumor suppressive effects and provide biomarker and therapeutic possibilities that deserve to be further explored.
Insights
Prostate cancer bone metastases show significantly lower microRNA levels. Downregulation of specific microRNAs like miRNA-23c and miRNA-4328 may reduce tumor suppression, offering potential biomarkers and therapies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Prostate cancer (PC) progression involves aberrant microRNA (miRNA) expression.
- Knowledge of miRNA profiles in metastatic PC, particularly bone metastasis, remains limited.
- Understanding miRNA changes is crucial for identifying therapeutic targets.
Purpose of the Study:
- To investigate differential miRNA expression in prostate cancer bone metastases.
- To identify specific downregulated miRNAs during PC progression.
- To explore the functional impact of miRNA-23c and miRNA-4328 on PC growth.
Main Methods:
- Microarray screening of 1510 miRNAs in bone metastases, localized PC, and benign prostate tissues.
- Quantitative polymerase chain reaction (qPCR) to validate miRNA downregulation.
- In vitro cell line experiments (22Rv1, PC-3) to assess miRNA overexpression effects.
- In vivo mouse models to evaluate tumor suppressive effects.
Main Results:
- Significant differential expression of miRNAs observed, with 75 decreased and 4 increased (p < 0.05).
- Consistent downregulation of specific miRNAs (e.g., miRNA-1, -23c, -143-3p, -4328) during progression from benign to metastatic PC.
- Overexpression of miRNA-23c and -4328 reduced PC cell growth in vitro, with miRNA-23c secreted in extracellular vesicles.
- No significant tumor suppressive effect of miRNA-23c was observed in vivo.
Conclusions:
- Prostate cancer bone metastases exhibit a marked reduction in miRNA levels.
- Downregulation of miRNAs, including miRNA-23c and -4328, correlates with disease progression and potential loss of tumor suppressive functions.
- These miRNAs represent potential biomarkers and therapeutic targets for advanced prostate cancer.
