Dicer ablation impairs prostate stem cell activity and causes prostate atrophy.

Area of Science:

• Molecular Biology
• Developmental Biology
• Urology

Background:

• Dicer is an RNase III enzyme vital for microRNA maturation.
• Dicer disruption in tissues impairs differentiation, induces apoptosis, and affects cellular function.
• MicroRNAs' role in prostate homeostasis and stem cell function requires further investigation.

Purpose of the Study:

• To investigate the role of microRNAs in prostate tissue function and homeostasis.
• To conditionally disrupt Dicer activity in mouse prostate stem and differentiated cells.

Main Methods:

• Conditional disruption of Dicer activity in mouse prostate using ARR2PB-Cre.
• Analysis of prostate size, mass, epithelial hypotrophy, apoptosis, and proliferation.
• Characterization of prostate stem cell activity using Lin(-)Sca-1(+)CD49f(high) (LSC) cells and sphere-forming assays.

Main Results:

• Dicer activity was disrupted in both basal/stem and luminal prostate cells.
• Dicer knockout prostates showed reduced size, mass, and epithelial hypotrophy.
• Increased apoptosis was observed in luminal cells, with paradoxical proliferation in both basal/stem and luminal cells.
• While LSC cells expanded, sphere-forming capacity decreased significantly in Dicer knockout prostates.
• Prostate spheres in knockout cultures were primarily derived from non-homologous recombination cells.

Conclusions:

• MicroRNAs are essential for prostate stem cell proliferation.
• Dicer-dependent microRNAs play a critical role in maintaining prostate homeostasis.
• Impaired microRNA processing affects prostate stem cell function and differentiation capacity.