Ribosome-targeting antibiotics as inhibitors of oncogenic microRNAs biogenesis: Old scaffolds for new perspectives in RNA targeting.
MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression at the post-transcriptional level. It is now well established that the overexpression of some miRNAs (oncogenic miRNAs) is responsible for initiation and progression of human cancers and the discovery of new molecules able to interfere with their production and/or function represents one of the most important challenges of current medicinal chemistry of RNA ligands. In this work, we studied the ability of 18 different antibiotics, known as prokaryotic ribosomal RNA, to bind to oncogenic miRNA precursors (stem-loop structured pre-miRNAs) in order to inhibit miRNAs production. In vitro inhibition, binding constants, thermodynamic parameters and binding sites were investigated and highlighted that aminoglycosides and tetracyclines represent interesting pre-miRNA ligands with the ability to inhibit Dicer processing.
Institute of Chemistry of Nice, UMR7272 CNRS-University Nice Sophia Antipolis, Parc Valrose, 06100 Nice, France.
Thi Phuong Anh
TP
Tran
Institute of Chemistry of Nice, UMR7272 CNRS-University Nice Sophia Antipolis, Parc Valrose, 06100 Nice, France.
Duc Duy
DD
Vo
Institute of Chemistry of Nice, UMR7272 CNRS-University Nice Sophia Antipolis, Parc Valrose, 06100 Nice, France.
Audrey
A
Di Giorgio
Institute of Chemistry of Nice, UMR7272 CNRS-University Nice Sophia Antipolis, Parc Valrose, 06100 Nice, France. Electronic address: maria.duca@unice.fr.
Maria
M
Duca
D000617:Aminoglycosides / Q000737:chemistry* / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001483:Base Sequence; D053487:DEAD-box RNA Helicases / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics; D043244:Ribonuclease III / Q000235:genetics; D012270:Ribosomes / Q000187:drug effects / Q000235:genetics; D013754:Tetracyclines / Q000737:chemistry* / Q000494:pharmacology*
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D035683:MicroRNAs; D013754:Tetracyclines; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
Antibiotics; Binding affinity; Inhibitors; Oncogenic microRNA; RNA recognition