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Updated: Jul 15, 2025
miRNA Expression Analyses in Prostate Cancer Clinical Tissues
Published on: September 8, 2015
Expression of microRNA-379 reduces metastatic spread of prostate cancer
James R Cassidy1, Gjendine Voss1, Kira Rosenkilde Underbjerg1
1Department of Laboratory Medicine, Division of Translational Cancer Research, Lund University, Lund, Sweden.
Introduction:
Prostate cancer (PCa) is the most common type of cancer in males, and the metastatic form is a leading cause of death worldwide. There are currently no curative treatments for this subset of patients. To decrease the mortality of this disease, greater focus must be placed on developing therapeutics to reduce metastatic spread. We focus on dissemination to the bone since this is both the most common site of metastatic spread and associated with extreme pain and discomfort for patients. Our strategy is to exploit microRNAs (miRNAs) to disrupt the spread of primary PCa to the bone.
Methods:
PCa cell lines were transduced to overexpress microRNA-379 (miR-379). These transduced PCa cells were assessed using cell growth, migration, colony formation and adhesion assays. We also performed in vivo intracardiac injections to look at metastatic spread in NSG mice. A cytokine array was also performed to identify targets of miR-379 that may drive metastatic spread.
Results:
PCa cells with increased levels of miR-379 showed a significant decrease in proliferation, migration, colony formation, and adhesion to bone cells in vitro. In vivo miR-379 overexpression in PC3 cells significantly decreased metastatic spread to bone and reduced levels of miR-379 were seen in patients with metastases. We identified GDF-15 to be secreted from osteoblasts when grown in conditioned media from PCa cells with reduced miR-379 levels.
Discussion:
Taken together, our in vitro and in vivo functional assays support a role for miR-379 as a tumour suppressor. A potential mechanism is unravelled whereby miR-379 deregulation in PCa cells affects the secretion of GDF-15 from osteoblasts which in turn facilitates the metastatic establishment in bone. Our findings support the potential role of miR-379 as a therapeutic solution for prostate cancer.
Insights
MicroRNA-379 (miR-379) acts as a tumor suppressor in prostate cancer, inhibiting its spread to the bone. Lower miR-379 levels in patients correlate with metastasis, suggesting its therapeutic potential.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Prostate cancer (PCa) metastasis, particularly to bone, is a major cause of mortality with limited treatment options.
- Developing therapeutics to inhibit PCa metastatic spread is crucial for improving patient outcomes.
- MicroRNAs (miRNAs) are key regulators of gene expression with potential roles in cancer progression.
Purpose of the Study:
- To investigate the role of microRNA-379 (miR-379) in suppressing prostate cancer metastasis to the bone.
- To identify potential therapeutic strategies targeting miR-379 for PCa treatment.
Main Methods:
- Overexpression of miR-379 in PCa cell lines.
- In vitro assays: cell growth, migration, colony formation, and adhesion.
- In vivo studies: intracardiac injections in NSG mice to assess metastatic spread.
- Cytokine array to identify miR-379 targets.
Main Results:
- Increased miR-379 levels significantly reduced PCa cell proliferation, migration, colony formation, and bone cell adhesion in vitro.
- In vivo, miR-379 overexpression decreased PCa bone metastasis.
- Reduced miR-379 levels were observed in patients with PCa metastases.
- GDF-15 secretion from osteoblasts was linked to reduced miR-379 levels in PCa cells.
Conclusions:
- miR-379 functions as a tumor suppressor in prostate cancer.
- miR-379 deregulation may influence GDF-15 secretion, facilitating bone metastasis.
- miR-379 holds potential as a therapeutic target for prostate cancer treatment.
