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Updated: Apr 18, 2026

Detection of miRNA Targets in High-throughput Using the 3'LIFE Assay
Published on: May 25, 2015
DICER-dependent biogenesis of let-7 miRNAs affects human cell response to DNA damage via targeting p21/p27
Bailong Liu1, Min Liu1, Jian Wang2
1Department of Radiation Oncology, The First Hospital of Jilin University, Changchun 130021, China Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA 30322, USA.
Abstract:
Recently, it was reported that knockdown of DICER reduced the ATM-dependent DNA damage response and homologous recombination repair (HRR) via decreasing DICER-generated small RNAs at the damage sites. However, we found that knockdown of DICER dramatically increased cell resistance to camptothecin that induced damage required ATM to facilitate HRR. This phenotype is due to a prolonged G1/S transition via decreasing DICER-dependent biogenesis of miRNA let-7, which increased the p21(Waf1/Cip1)/p27(Kip1) levels and resulted in decreasing the HRR efficiency. These results uncover a novel function of DICER in regulating the cell cycle through miRNA biogenesis, thus affecting cell response to DNA damage.
Insights
Knockdown of DICER enhances cell resistance to DNA damage by prolonging G1/S transition, affecting microRNA let-7 levels and DNA repair efficiency. This study reveals DICER
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- DICER is involved in small RNA generation and DNA damage response.
- Previous studies suggested DICER knockdown impairs DNA repair.
Purpose of the Study:
- To investigate the role of DICER in cellular response to DNA damage.
- To elucidate the mechanism by which DICER affects DNA repair and cell cycle progression.
Main Methods:
- Cell culture and treatment with camptothecin.
- Western blotting to assess protein levels (p21, p27).
- Analysis of cell cycle progression and DNA repair efficiency.
Main Results:
- DICER knockdown increased resistance to camptothecin-induced DNA damage.
- This resistance was linked to a prolonged G1/S transition due to decreased microRNA let-7 biogenesis.
- Reduced microRNA let-7 led to increased p21(Waf1/Cip1)/p27(Kip1) levels, impairing homologous recombination repair (HRR).
Conclusions:
- DICER plays a novel role in regulating cell cycle progression via microRNA biogenesis.
- This regulation impacts cellular responses to DNA damage and repair mechanisms.
- The findings challenge previous understandings of DICER's function in DNA damage response.
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