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

Shun-Tsung Chen; Chien-Hung Huang; Victor C Kok; Chi-Ying F Huang; Jin-Shuei Ciou; Jeffrey J P Tsai; Nilubon Kurubanjerdjit; Ka-Lok Ng

doi:10.1142/S0219720016500438

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

J Bioinform Comput Biol. 2017 Feb;15(1):1650043. doi: 10.1142/S0219720016500438. Epub 2016 Dec 22.

Authors

Shun-Tsung Chen¹, Chien-Hung Huang², Victor C Kok^{1

3}, Chi-Ying F Huang⁴, Jin-Shuei Ciou¹, Jeffrey J P Tsai¹, Nilubon Kurubanjerdjit⁵, Ka-Lok Ng^{1

6}

Affiliations

¹ * Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan 41354, R.O.C.
² † Department of Computer Science and Information Engineering, National Formosa University, Yun-Lin, Taiwan 63205, R.O.C.
³ ‡ Division of Medical Oncology, Kuang Tien General Hospital Cancer, Center Taichung, Taiwan 43303, R.O.C.
⁴ § Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan 112, R.O.C.
⁵ ¶ School of Information Technology, Mae Fah Luang University, Chiang Rai, Thailand 57100, Thailand.
⁶ ∥ Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan 40402, R.O.C.

PMID: 28150521
DOI: 10.1142/S0219720016500438

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.

Keywords: Cardiovascular disease; Gene Ontology enrichment analysis; antimiR; differentially expressed gene; drug repurposing; microRNA; oxidized low-density lipoprotein; time-course microarray; vascular smooth muscle cell.

MeSH terms

Cardiovascular Diseases / drug therapy
Cardiovascular Diseases / pathology
Cluster Analysis
Drug Discovery
Drug Repositioning / methods*
Gene Expression Regulation / drug effects*
Gene Ontology
Humans
Lipoproteins, LDL / genetics*
MicroRNAs*
Molecular Targeted Therapy
Muscle, Smooth, Vascular / cytology

Substances

Lipoproteins, LDL
MicroRNAs
oxidized low density lipoprotein