The tuberculosis drug streptomycin as a potential cancer therapeutic: inhibition of miR-21 function by directly targeting its precursor.

Dedicated to Professor Samir K. Brahmachari on the occasion of his 60th birthdayMicroRNAs (miRNAs) play crucial roles in regulating geneexpression in many cellular contexts. Deregulation ofmiRNAs has been implicated in a number of diseaseconditions and thus, small molecules that can modulatemature miRNA levels in cells can have immense therapeuticpotential. Aminoglycosides, mostly used as antibiotics, areknown specifically to bind to certain RNA secondarystructures. Herein, we report that one such aminoglycoside,streptomycin,candown-regulatethelevelsofmaturemiR-21,a miRNA with roles in a variety of cancers. We suggest thatstreptomycin down-regulates miR-21 by binding to pre-miRNA (its precursor) and blocking the function of theDicer enzyme, an essential step in miRNA maturation.MicroRNAs are a class of endogenous noncoding RNAsthat act post-transcriptionally to target mRNAs for transla-tional repression, cleavage, and destabilization.

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