Exploring Small‐Molecule Modulators of Precursor miRNA Processing Associated With Glycolysis

MicroRNAs (miRNAs) are single-stranded noncoding RNAs with 17-25 nucleotides in length that modulate gene expression by binding to specific mRNAs. They play a critical role in the maintenance and regulation of various physiological functions. In humans, approximately 2000 miRNAs have been identified, and they are predicted to regulate the expression of approximately 60% of all protein-coding genes. Given their broad regulatory role, small molecules targeting miRNA biogenesis can induce significant changes in cellular function. In this study, we conducted a high-throughput screening of a chemical library comprising 2320 known compounds to identify small-molecule binders to target precursor miRNAs (pre-miRNAs) using a fluorescent indicator displacement (FID) assay. Two sequential screenings using distinct fluorescent indicators identified 34 candidate compounds capable of interacting with the target pre-miRNAs. The binding of these candidate compounds to the target pre-miRNAs was further evaluated by surface plasmon resonance (SPR) analysis. We subsequently evaluated the effects of the candidate compounds on the Dicer-mediated processing of the target pre-miRNAs, leading to the identification of several compounds with the inhibitory effect.