title: Integrated analysis of miRNA and mRNA gene expression microarrays: Influence on platelet reactivity, clopidogrel response and drug-induced toxicity.
abstract: Genetic and epigenetic variability may influence the efficacy and safety of antiplatelet therapies, including clopidogrel. Therefore, the miRNA-mRNA interactions and drug toxicity were investigated in silico using available microarray data. Expressions profiles of platelet miRNA (GSE59488) from acute coronary syndrome and mRNA in peripheral blood cells (GSE32226) from coronary artery disease patients were used to miRNA-target mRNA integrated analysis by Ingenuity Pathways Analysis 6 software (IPA). Results showed that ST13 mRNA is regulated by hsa-miR-107 (miR-103-3p); BTNL3 and CFD mRNAs are regulated by hsa-miR-4701-3p (miR-1262); SLC7A8 is regulated by hsa-miR-145-5p (miR-145-5p); and SENP5 mRNA is regulated by hsa-miR-15b-5p (miR-16-5p) and hsa-miR-26a-5p (miR-26a-5p). Drug toxicity IPA tool showed that these miRNAs/mRNAs are associated with clopidogrel-related liver and renal injury. In conclusion, these results demonstrate that differential expression of miRNAs in platelets and interactions with their target mRNAs are associated with variability in platelet reactivity, clopidogrel response and drug-induced toxicity.
authors.affiliation: Department of Clinical and Toxicological Analysis, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors.forename: Renata Caroline Costa de
authors.initials: RCC
authors.lastname: Freitas
authors.affiliation: Department of Clinical and Toxicological Analysis, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors.forename: Raul Hernandes
authors.initials: RH
authors.lastname: Bortolin
authors.affiliation: Department of Clinical and Toxicological Analysis, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors.forename: Mariana Borges
authors.initials: MB
authors.lastname: Lopes
authors.affiliation: School of Pharmaceutical Sciences, University of Sao Paulo, São Paulo, Brazil.
authors.forename: Mario Hiroyuki
authors.initials: MH
authors.lastname: Hirata
authors.affiliation: School of Pharmaceutical Sciences, University of Sao Paulo, São Paulo, Brazil.
authors.forename: Rosario Dominguez Crespo
authors.initials: RDC
authors.lastname: Hirata
authors.affiliation: Department of Clinical and Toxicological Analysis, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors.forename: Vivian Nogueira
authors.initials: VN
authors.lastname: Silbiger
authors.affiliation: Department of Clinical and Toxicological Analysis, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil. Electronic address: andre.luchessi@outlook.com.
authors.forename: André Ducati
authors.initials: AD
authors.lastname: Luchessi
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D000077144:Clopidogrel; D030561:Databases, Nucleic Acid; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000096:biosynthesis*; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; D000077144:Clopidogrel; D013988:Ticlopidine
keywords: Antiplatelet therapy; Bioinformatics; Pharmacogenomics; Target gene; miRNA