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Updated: May 11, 2026

miRNA Expression Analyses in Prostate Cancer Clinical Tissues
Published on: September 8, 2015
Essential role of NADPH oxidase-dependent reactive oxygen species generation in regulating microRNA-21 expression and
Sarvesh Jajoo1, Debashree Mukherjea, Tejbeer Kaur
11 Department of Pharmacology, Southern Illinois University School of Medicine , Springfield, Illinois.
Aims:
Oncogenic microRNAs (miRs) promote tumor growth and invasiveness. One of these, miR-21, contributes to carcinogenesis in prostate and other cancers. In the present study, we tested the hypothesis that NADPH oxidase-dependent reactive oxygen species (ROS) regulate the expression and function of miR-21 and its target proteins, maspin and programmed cell death 4 (PDCD4), in prostate cancer cells.
Results:
The highly aggressive androgen receptor negative PC-3M-MM2 prostate cancer cells demonstrated high expression of miR-21 and p47(phox) (an essential subunit of NADPH oxidase). Using loss-of-function strategy, we showed that transfection of PC-3M-MM2 cells with anti-miR-21- and p47(phox) siRNA (si-p47(phox)) led to reduced expression of miR-21 with concurrent increase in maspin and PDCD4, and decreased the invasiveness of the cells. Tail-vein injections of anti-miR-21- and si-p47(phox)-transfected PC-3M-MM2 cells in severe combined immunodeficient mice reduced lung metastases. Clinical samples from patients with advanced prostate cancer expressed high levels of miR-21 and p47(phox), and low expression of maspin and PDCD4. Finally, ROS activated Akt in these cells, the inhibition of which reduced miR-21 expression.
Innovation:
The levels of NADPH oxidase-derived ROS are high in prostate cancer cells, which have been shown to be involved in their growth and migration. This study demonstrates that ROS produced by this pathway is essential for the expression and function of an onco-miR, miR-21, in androgen receptor-negative prostate cancer cells.
Conclusion:
These data demonstrate that miR-21 is an important target of ROS, which contributes to the highly invasive and metastatic phenotype of prostate cancer cells.
Insights
Reactive oxygen species (ROS) drive prostate cancer progression by regulating miR-21. Inhibiting ROS or miR-21 reduces cancer cell invasiveness and metastasis, offering new therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Oncogenic microRNAs (miRs) like miR-21 are implicated in tumor growth and metastasis.
- NADPH oxidase-derived reactive oxygen species (ROS) are elevated in prostate cancer and influence cell behavior.
- miR-21 targets tumor suppressors maspin and programmed cell death 4 (PDCD4).
Purpose of the Study:
- To investigate the role of NADPH oxidase-dependent ROS in regulating miR-21 expression and function in prostate cancer cells.
- To determine the impact of ROS-mediated miR-21 regulation on its target proteins, maspin and PDCD4.
- To assess the therapeutic potential of targeting the ROS-miR-21 axis in prostate cancer.
Main Methods:
- Utilized androgen receptor-negative PC-3M-MM2 prostate cancer cell line.
- Employed loss-of-function strategies including anti-miR-21 and p47(phox) siRNA (si-p47(phox)) transfections.
- Assessed cell invasiveness and lung metastasis in severe combined immunodeficient mice models.
- Analyzed clinical samples from advanced prostate cancer patients.
Main Results:
- High expression of miR-21 and p47(phox) was observed in aggressive prostate cancer cells and patient samples.
- Inhibition of miR-21 and p47(phox) reduced miR-21 levels, increased maspin and PDCD4 expression, and decreased cell invasiveness.
- Targeted inhibition significantly reduced lung metastasis in vivo.
- ROS were found to activate Akt, and its inhibition decreased miR-21 expression.
Conclusions:
- ROS are essential regulators of miR-21 expression and function in prostate cancer.
- miR-21 acts as a key mediator of ROS-induced invasiveness and metastasis.
- The ROS-miR-21 pathway represents a potential therapeutic target for advanced prostate cancer.
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