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Updated: May 12, 2026

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
De-regulated microRNAs in pediatric cancer stem cells target pathways involved in cell proliferation, cell cycle and
Patricia C Sanchez-Diaz1, Tzu-Hung Hsiao, Judy C Chang
1Greehey Children's Cancer Research Institute, University of Texas Health Science Center San Antonio, San Antonio, Texas, United States of America.
Background:
microRNAs (miRNAs) have been implicated in the control of many biological processes and their deregulation has been associated with many cancers. In recent years, the cancer stem cell (CSC) concept has been applied to many cancers including pediatric. We hypothesized that a common signature of deregulated miRNAs in the CSCs fraction may explain the disrupted signaling pathways in CSCs.
Methodology/Results:
Using a high throughput qPCR approach we identified 26 CSC associated differentially expressed miRNAs (DEmiRs). Using BCmicrO algorithm 865 potential CSC associated DEmiR targets were obtained. These potential targets were subjected to KEGG, Biocarta and Gene Ontology pathway and biological processes analysis. Four annotated pathways were enriched: cell cycle, cell proliferation, p53 and TGF-beta/BMP. Knocking down hsa-miR-21-5p, hsa-miR-181c-5p and hsa-miR-135b-5p using antisense oligonucleotides and small interfering RNA in cell lines led to the depletion of the CSC fraction and impairment of sphere formation (CSC surrogate assays).
Conclusion:
Our findings indicated that CSC associated DEmiRs and the putative pathways they regulate may have potential therapeutic applications in pediatric cancers.
Insights
Deregulation of microRNAs (miRNAs) is linked to pediatric cancers. This study identified specific miRNAs targeting key pathways, suggesting potential therapeutic strategies for pediatric cancer stem cells (CSCs).
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) play crucial roles in biological processes, and their dysregulation is associated with various cancers.
- The cancer stem cell (CSC) model is increasingly recognized in pediatric cancers.
- A common miRNA signature in CSCs may underlie disrupted signaling pathways.
Purpose of the Study:
- To identify deregulated miRNAs within the cancer stem cell (CSC) fraction in pediatric cancers.
- To elucidate the signaling pathways regulated by these CSC-associated miRNAs.
- To explore potential therapeutic applications of these findings.
Main Methods:
- High-throughput quantitative PCR (qPCR) was employed to identify differentially expressed miRNAs (DEmiRs) in CSCs.
- The BCmicrO algorithm was used to predict potential targets of identified DEmiRs.
- Pathway analysis (KEGG, Biocarta, Gene Ontology) was performed on predicted targets.
Main Results:
- 26 CSC-associated DEmiRs were identified.
- 865 potential CSC-associated DEmiR targets were predicted.
- Enriched pathways included cell cycle, cell proliferation, p53, and TGF-beta/BMP signaling.
- Knockdown of specific miRNAs (hsa-miR-21-5p, hsa-miR-181c-5p, hsa-miR-135b-5p) reduced CSC fraction and sphere formation.
Conclusions:
- CSC-associated DEmiRs and their regulated pathways show promise for therapeutic intervention in pediatric cancers.
- Targeting these miRNAs could offer novel treatment strategies for pediatric malignancies.
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