Identification of aminosulfonylarylisoxazole as microRNA-31 regulators.

ABSTRACT

The discovery of small-molecule regulators of microRNAs remains challenging, but a few have been reported. Herein, we describe small-molecule inhibitors of miR-31, a tumor-associated microRNA (miRNA), identified by high-throughput screening using a cell-based reporter assay. Aminosulfonylarylisoxazole compounds exhibited higher specificity for miR-31 than for six other miRNAs, i.e., miR-15a, miR-16, miR-21, miR-92a-1, miR-146a, and miR-155, and increased the expression of miR-31 target genes. The down-regulation of mature miR-31 was observed, while its precursor form increased following treatment with the compounds. Thus, the compounds may target the processing of pre-miR-31 into mature miR-31 and thereby inhibit the production of mature miR-31.