Drug repurposing and therapeutic anti-microRNA predictions for inhibition of oxidized low-density lipoprotein-induced vascular smooth muscle cell-associated diseases.
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.
* Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan 41354, R.O.C.
Shun-Tsung
ST
Chen
† Department of Computer Science and Information Engineering, National Formosa University, Yun-Lin, Taiwan 63205, R.O.C.
Chien-Hung
CH
Huang
* Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan 41354, R.O.C.|‡ Division of Medical Oncology, Kuang Tien General Hospital Cancer, Center Taichung, Taiwan 43303, R.O.C.
Victor C
VC
Kok
§ Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan 112, R.O.C.
Chi-Ying F
CF
Huang
* Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan 41354, R.O.C.
Jin-Shuei
JS
Ciou
* Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan 41354, R.O.C.
Jeffrey J P
JJ
Tsai
¶ School of Information Technology, Mae Fah Luang University, Chiang Rai, Thailand 57100, Thailand.
Nilubon
N
Kurubanjerdjit
* Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan 41354, R.O.C.|∥ Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan 40402, R.O.C.
Ka-Lok
http://orcid.org/0000-0001-6315-6326
KL
Ng
D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000473:pathology; D016000:Cluster Analysis; D055808:Drug Discovery; D058492:Drug Repositioning / Q000379:methods*; D005786:Gene Expression Regulation / Q000187:drug effects*; D063990:Gene Ontology; D006801:Humans; D008077:Lipoproteins, LDL / Q000235:genetics*; D035683:MicroRNAs; D058990:Molecular Targeted Therapy; D009131:Muscle, Smooth, Vascular / Q000166:cytology
D008077:Lipoproteins, LDL; D035683:MicroRNAs; C099252:oxidized low density lipoprotein
Cardiovascular disease; Gene Ontology enrichment analysis; antimiR; differentially expressed gene; drug repurposing; microRNA; oxidized low-density lipoprotein; time-course microarray; vascular smooth muscle cell