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Chembiochem. 2018 Jan 4;19(1):43-47. doi: 10.1002/cbic.201700581. Epub 2017 Nov 22.

Bleomycin Can Cleave an Oncogenic Noncoding RNA.

Author information

1
Department 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.

KEYWORDS:

bleomycin; chemical biology; noncoding RNA; nucleic acids; small molecules

PMID:
29084369
PMCID:
PMC5810124
DOI:
10.1002/cbic.201700581
[Indexed for MEDLINE]
Free PMC Article

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