title: MiRNA-145 Regulates the Development of Congenital Heart Disease Through Targeting FXN.
abstract: Congenital heart disease (CHD) is the leading cause of death in infants in the world. The study of CHDs has come a long way since their classification and description. Although transcriptional programmes that are impaired in individuals with CHDs are being identified, the mechanisms of how these deficiencies translate to a structural defect are unknown. In this study, using high-throughput microarray analysis and molecular network analysis, FXN was identified to be the most differentially expressed key gene in CHD. By TargetScan analysis, we predicted FXN was the target gene of miRNA-145 and miRNA-182. Through real-time PCR analysis of clinical samples and experiments in cell lines, we confirmed that miRNA-145 but not miRNA-182 directly binds to the 3' UTR region of FXN and negatively regulates its expression. We further found that through targeting FXN, miRNA-145 regulates apoptosis and mitochondrial function. In general, our study confirmed the differentially expressed FXN regulates the development of CHD and the differential expression was under the control of miRNA-145. These results might provide new insight into the understanding of the CHD pathogenesis and may facilitate further therapeutic studies.
authors.affiliation: Department of Cardiology, Xi'an Children's Hospital, No. 69, Xiju RD, Lianhu District, Xi'an, 710003, Shaanxi, China. xawanglei@163.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Xi'an Children's Hospital, No. 69, Xiju RD, Lianhu District, Xi'an, 710003, Shaanxi, China.
authors.forename: Danqiu
authors.initials: D
authors.lastname: Tian
authors.affiliation: Department of Cardiology, Xi'an Children's Hospital, No. 69, Xiju RD, Lianhu District, Xi'an, 710003, Shaanxi, China.
authors.forename: Jihua
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Cardiology, Xi'an Children's Hospital, No. 69, Xiju RD, Lianhu District, Xi'an, 710003, Shaanxi, China.
authors.forename: Haijian
authors.initials: H
authors.lastname: Xing
authors.affiliation: Department of Cardiology, Xi'an Children's Hospital, No. 69, Xiju RD, Lianhu District, Xi'an, 710003, Shaanxi, China.
authors.forename: Min
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Cardiology, Xi'an Children's Hospital, No. 69, Xiju RD, Lianhu District, Xi'an, 710003, Shaanxi, China.
authors.forename: Juanli
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Xi'an Children's Hospital, No. 69, Xiju RD, Lianhu District, Xi'an, 710003, Shaanxi, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Jian
authors.affiliation: Department of Cardiology, Xi'an Children's Hospital, No. 69, Xiju RD, Lianhu District, Xi'an, 710003, Shaanxi, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002681:China; D005260:Female; D053263:Gene Regulatory Networks; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D033862:Iron-Binding Proteins / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D046228:Microarray Analysis; D000096923:Frataxin
chemical_list: D020413:3' Untranslated Regions; D033862:Iron-Binding Proteins; D035683:MicroRNAs; D000096923:Frataxin; C541010:MIRN145 microRNA, human
keywords: Congenital heart disease; FXN; MiRNA-145