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MicroRNA expression profiling involved in doxorubicin-induced cardiotoxicity using high-throughput deep-sequencing analysis

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机构: [1]Departments of Oncology,Tongren Hospital, Shanghai Jiao Tong University School of Medicine [2]Departments of Cardiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine [3]Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200336, P.R. China [4]Present address: Fuzhou Berrygenomics Inc., 33 Donghu Road, Fuzhou, Fujian 350003, P.R. China
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关键词: doxorubicin microRNA cardiomyocyte cardiotoxicity

摘要:
MicroRNAs (miRNAs/miRs) are sensitive biomarkers and endogenous repressors of gene expression by decreasing mRNA stability and interfering with mRNA translation. Despite a number of investigations revealing the dysregulation of miRNA expression associated with cardiotoxicity induced by doxorubicin (Dox), perturbation of miRNAs directly resulting from Dox at early stage in cardiomyocytes and the target gene interaction remain largely unknown. In the present study, high-throughput deep-sequencing was used to analyze changes in global miRNA expression in H9c2 cardiomyocytes exposed to 5 mu g/ml Dox for 0, 12 or 24 h. Compared with the 0-h time point, the expression levels of 386 unique miRNAs were altered. Based on miRNA expression and fold-change, the target genes of 76 selected miRNAs were further analyzed using gene interaction networks and pathway enrichment analysis. These miRNAs were involved in the regulation of different pathways, whose functions included apoptosis, cell proliferation, extracellular matrix remodeling, oxidative stress and lipid metabolism. These differentially expressed miRNAs included let-7 family, miR-29b-3p, miR-378-3/5p, miR-351-3p, miR-664-3p, miR-455-3p, miR-298-3p, miR-702-5p, miR-128-1-5p, miR-671 and miR-421-5p. The present data indicated that global wide miRNA profiling in Dox-induced cardiomyocytes may provide a novel mechanistic insight into understanding Dox-induced heart failure and cardiotoxicity, as well as novel biomarkers and therapeutic targets.

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出版当年[2020]版:
大类 | 4 区 医学
小类 | 4 区 肿瘤学
最新[2023]版:
大类 | 4 区 医学
小类 | 4 区 肿瘤学
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出版当年[2019]版:
Q3 ONCOLOGY
最新[2023]版:
Q3 ONCOLOGY

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第一作者机构: [1]Departments of Oncology,Tongren Hospital, Shanghai Jiao Tong University School of Medicine
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通讯机构: [1]Departments of Oncology,Tongren Hospital, Shanghai Jiao Tong University School of Medicine [2]Departments of Cardiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine [*1]Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111 Xianxia Road, Shanghai 200336, P.R. China [*2]Department of Cardiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111 Xianxia Road, Shanghai 200336, P.R. China
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