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Updated: Feb 19, 2026

Oropharyngeal Administration of Bleomycin in the Murine Model of Pulmonary Fibrosis
Published on: May 9, 2025
Bleomycin Can Cleave an Oncogenic Noncoding RNA
Alicia J Angelbello1, Matthew D Disney1
1Department of Chemistry, The Scripps Research Institute, 110 Scripps Way, Jupiter, FL, 33458, USA.
Abstract:
Noncoding RNAs are pervasive in cells and contribute to diseases such as cancer. A question in biomedical research is whether noncoding RNAs are targets of medicines. Bleomycin is a natural product that cleaves DNA; however, it is known to cleave RNA in vitro. Herein, an in-depth analysis of the RNA cleavage preferences of bleomycin A5 is presented. Bleomycin A5 prefers to cleave RNAs with stretches of AU base pairs. Based on these preferences and bioinformatic analysis, the microRNA-10b hairpin precursor was identified as a potential substrate for bleomycin A5. Both in vitro and cellular experiments demonstrated cleavage. Importantly, chemical cleavage by bleomycin A5 in the microRNA-10b hairpin precursors occurred near the Drosha and Dicer enzymatic processing sites and led to destruction of the microRNA. Evidently, oncogenic noncoding RNAs can be considered targets of cancer medicines and might elicit their pharmacological effects by targeting noncoding RNA.
Insights
Bleomycin A5 cleaves RNA, specifically targeting microRNA-10b precursors near key processing sites. This demonstrates that oncogenic noncoding RNAs can be targeted by cancer drugs for therapeutic effects.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Noncoding RNAs play crucial roles in cellular functions and disease, including cancer.
- The potential of noncoding RNAs as therapeutic targets remains an active area of biomedical research.
- Bleomycin, a DNA-cleaving agent, has demonstrated in vitro RNA cleavage capabilities.
Purpose of the Study:
- To investigate the RNA cleavage preferences of bleomycin A5.
- To identify specific noncoding RNA targets susceptible to bleomycin A5-mediated cleavage.
- To evaluate the therapeutic potential of targeting noncoding RNAs with bleomycin A5.
Main Methods:
- In vitro analysis of bleomycin A5's RNA cleavage activity and sequence preferences.
- Bioinformatic identification of potential microRNA substrates.
- In vitro and cellular experiments to confirm bleomycin A5-mediated cleavage of microRNA-10b hairpin precursor.
- Assessment of the impact of cleavage on microRNA processing and function.
Main Results:
- Bleomycin A5 exhibits a preference for cleaving RNA sequences rich in AU base pairs.
- The microRNA-10b hairpin precursor was identified as a susceptible substrate for bleomycin A5.
- Both in vitro and cellular studies confirmed bleomycin A5-induced cleavage of the microRNA-10b precursor.
- Cleavage occurred near Drosha and Dicer processing sites, leading to microRNA degradation.
Conclusions:
- Oncogenic noncoding RNAs can be effectively targeted by cancer therapeutics like bleomycin.
- Bleomycin A5 demonstrates a mechanism for pharmacologically impacting noncoding RNA pathways.
- Targeting noncoding RNAs represents a viable strategy for cancer drug development.
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MicroRNAs
MicroRNAs
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lncRNA - Long Non-coding RNAs
lncRNA - Long Non-coding RNAs

