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Updated: Mar 15, 2026
MicroRNA Detection in Prostate Tumors by Quantitative Real-time PCR qPCR
Published on: May 16, 2012
MiR-26a and miR-138 block the G1/S transition by targeting the cell cycle regulating network in prostate cancer cells
Kati Erdmann1, Knut Kaulke2, Christiane Rieger2
1Department of Urology, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany. kati.erdmann@uniklinikum-dresden.de.
Purpose:
The tumor-suppressive microRNAs miR-26a and miR-138 are significantly down-regulated in prostate cancer (PCa) and have been identified as direct regulators of enhancer of zeste homolog 2 (EZH2), which is a known oncogene in PCa. In the present study, the influence of miR-26a and miR-138 on EZH2 and cellular function including the impact on the cell cycle regulating network was evaluated in PCa cells.
Methods:
PC-3 and DU-145 PCa cells were transfected with 100 nM of miRNA mimics, siRNA against EZH2 (siR-EZH2) or control constructs for 4 h. Analyses of gene expression and cellular function were conducted 48 h after transfection.
Results:
Both miRNAs influenced the EZH2 expression and activity only marginally, whereas siR-EZH2 led to a notable decrease of the EZH2 expression and activity. Both miRNAs inhibited short- and/or long-term proliferation of PCa cells but showed no effect on viability and apoptosis. In PC-3 cells, miR-26a and miR-138 caused a significant surplus of cells in the G0/G1 phase of 6 and 12 %, respectively, thus blocking the G1/S-phase transition. Treatment with siR-EZH2 was without substantial influence on cellular function and cell cycle. Therefore, alternative target genes involved in cell cycle regulation were identified in silico. MiR-26a significantly diminished the expression of its targets CCNE1, CCNE2 and CDK6, whereas CCND1, CCND3 and CDK6 were suppressed by their regulator miR-138.
Conclusions:
The present findings suggest an anti-proliferative role for miR-26a and miR-138 in PCa by blocking the G1/S-phase transition independent of EZH2 but via a concerted inhibition of crucial cell cycle regulators.
Insights
MicroRNAs miR-26a and miR-138 inhibit prostate cancer cell proliferation by blocking cell cycle progression. These tumor suppressors act independently of EZH2, targeting key cell cycle regulators instead.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Prostate cancer (PCa) is associated with down-regulation of tumor-suppressive microRNAs, including miR-26a and miR-138.
- These microRNAs are known regulators of enhancer of zeste homolog 2 (EZH2), an oncogene implicated in PCa progression.
Purpose of the Study:
- To investigate the functional impact of miR-26a and miR-138 on EZH2 expression and activity in PCa cells.
- To evaluate the effects of these microRNAs on PCa cell proliferation, viability, apoptosis, and cell cycle regulation.
Main Methods:
- PC-3 and DU-145 PCa cells were transfected with miRNA mimics or siRNA against EZH2.
- Gene expression, cellular proliferation, viability, apoptosis, and cell cycle distribution were analyzed 48 hours post-transfection.
Main Results:
- miR-26a and miR-138 showed minimal influence on EZH2 expression but significantly inhibited PCa cell proliferation.
- These miRNAs induced cell cycle arrest at the G0/G1 phase, independent of EZH2.
- In silico analysis identified CCNE1, CCNE2, CDK6 (for miR-26a) and CCND1, CCND3, CDK6 (for miR-138) as direct targets involved in cell cycle regulation.
Conclusions:
- miR-26a and miR-138 exert an anti-proliferative effect in prostate cancer.
- Their mechanism involves blocking the G1/S-phase transition by inhibiting critical cell cycle regulators, independent of EZH2.
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