Cisplatin binds to pre-miR-200b and impairs its processing to mature microRNA

 Roman Mezencev, Roger Wartell

Abstract:

Cisplatin is an important anticancer drug with a complex mode of action, a variety of possible targets, and numerous resistance mechanisms. While genomic DNA has traditionally been considered to be its most critical anticancer target, several lines of evidence suggest that various RNAs and other biomolecules may play a role in its anticancer mode of action. In this report we demonstrate that cisplatin modifies pre-miR-200b, impairs its processing to mature miRNA, and down-regulates its expression in ovarian cancer cells. Considering the role of miR-200b in epithelial-to-mesenchymal transition and cancer chemosensitivity, cisplatin-induced modification of pre-miR-200b and subsequent deregulation of mature miR-200b may, depending on cell context, limit anticancer activity of this important anticancer drug. More generally, precursor miRNAs may be important targets of cisplatin and play a role in this drug’s anticancer activity or modulate cell responses to this drug.