title: MicroRNAs as potential biomarkers for doxorubicin-induced cardiotoxicity.
abstract: Anthracyclines, such as doxorubicin, are well-established, highly efficient anti-neoplastic drugs used for treatment of a variety of cancers, including solid tumors, leukemia, lymphomas, and breast cancer. The successful use of doxorubicin has, however, been hampered by severe cardiotoxic side-effects. In order to prevent or reverse negative side-effects of doxorubicin, it is important to find early biomarkers of heart injury and drug-induced cardiotoxicity. The high stability under extreme conditions, presence in various body fluids, and tissue-specificity, makes microRNAs very suitable as clinical biomarkers. The present study aimed towards evaluating the early and late effects of doxorubicin on the microRNA expression in cardiomyocytes derived from human pluripotent stem cells. We report on several microRNAs, including miR-34a, miR-34b, miR-187, miR-199a, miR-199b, miR-146a, miR-15b, miR-130a, miR-214, and miR-424, that are differentially expressed upon, and after, treatment with doxorubicin. Investigation of the biological relevance of the identified microRNAs revealed connections to cardiomyocyte function and cardiotoxicity, thus supporting the findings of these microRNAs as potential biomarkers for drug-induced cardiotoxicity.
authors.affiliation: Systems Biology Research Center, School of Bioscience, University of Skövde, Box 408 Kanikegränd 3A, SE-541 28, Skövde, Sweden; Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, University of Gothenburg, Sahlgrenska University Hospital, SE-413 45, Gothenburg, Sweden. Electronic address: gustav.holmgren@his.se.
authors.forename: Gustav
authors.initials: G
authors.lastname: Holmgren
authors.affiliation: Systems Biology Research Center, School of Bioscience, University of Skövde, Box 408 Kanikegränd 3A, SE-541 28, Skövde, Sweden. Electronic address: jane.synnergren@his.se.
authors.forename: Jane
authors.initials: J
authors.lastname: Synnergren
authors.affiliation: Takara Bio Europe AB, Arvid Wallgrens Backe 20, SE-413 46, Gothenburg, Sweden. Electronic address: Christian.andersson@takara-clontech.eu.
authors.forename: Christian X
authors.initials: CX
authors.lastname: Andersson
authors.affiliation: Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, University of Gothenburg, Sahlgrenska University Hospital, SE-413 45, Gothenburg, Sweden. Electronic address: anders.lindahl@clinchem.gu.se.
authors.forename: Anders
authors.initials: A
authors.lastname: Lindahl
authors.affiliation: Systems Biology Research Center, School of Bioscience, University of Skövde, Box 408 Kanikegränd 3A, SE-541 28, Skövde, Sweden; AstraZeneca Gothenburg, CVMD GMed, GMD, Pepparedsleden 1, SE-430 51, Mölndal, Sweden. Electronic address: peter.sartipy@his.se.
authors.forename: Peter
authors.initials: P
authors.lastname: Sartipy
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D015415:Biomarkers / Q000378:metabolism; D066126:Cardiotoxicity / Q000209:etiology / Q000235:genetics*; D002478:Cells, Cultured; D004317:Doxorubicin / Q000633:toxicity*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D015415:Biomarkers; D035683:MicroRNAs; D004317:Doxorubicin
keywords: Biomarkers; Cardiomyocytes; Doxorubicin; Human pluripotent stem cells; MicroRNA; Toxicity