Drug repurposing and therapeutic anti-microRNA predictions for inhibition of oxidized low-density lipoprotein-induced vascular smooth muscle cell-associated diseases

Abstract

Drug repurposing is a new method for disease treatments, which accelerates the identification of new uses for existing drugs with minimal side effects for patients. MicroRNA-based therapeutics are a class of drugs that have been used in gene therapy following the FDA's approval of the first anti-sense therapy. This study examines the effects of oxLDL on vascular smooth muscle cells (VSMCs) and identifies potential drugs and antimiRs for treating VSMC-associated diseases. The Connectivity Map (cMap) database is utilized to identify potential new uses of existing drugs. The success of the identifications was supported by MTT assay, clonogenic assay and clinical trial data. Specifically, 37 drugs, some of which are undergoing clinical trials, were identified. Three of the identified drugs exhibit IC50 activities. Among the 37 drugs' targets, three differentially expressed genes (DEGs) are identified as drug targets by using both the DrugBank and the NCBI PubChem Compound databases. Also, one DEG, DNMT1, which is regulated by 17 miRNAs, where these miRNAs are potential targets for developing antimiR-based miRNA therapy, is found.