title: Molecular dysfunctions in acute myeloid leukemia revealed by integrated analysis of microRNA and transcription factor.
abstract: Acute myeloid leukemia (AML) is a heterogenic hematological malignancy with pathogenesis that has yet to be elucidated. MicroRNAs (miRNAs) and transcription factors (TFs) are two major regulators of gene expression, which may play important roles in the etiology of AML. However, the global regulation of gene expression in AML, involving miRNAs and TFs, still remains elusive. To characterize the global role of miRNAs and TFs in AML pathogenesis, large scale expression profiling of miRNA and TF was performed using miRNA sequencing and TF array technology, respectively, and validated by qPCR. In the present study, 308 miRNAs and 84 TFs were identified to be differentially expressed (fold-change ≥2.0) in AML samples relative to their controls. After integrating the expression profiling data into bioinformatic analysis, we identified 1,462 miRNA-gene pairs, 982 TF-gene pairs and 296 TF-miRNA pairs. By merging these regulatory relations together, we constructed a comprehensive AML-specific miRNA-TF regulatory network. In this network, we identified 22 hub miRNAs and 11 hub TFs. KEGG pathway analysis showed that the network nodes were significantly enriched in 33 different pathways, of which the AML pathway was the most significant. After analyzing the topology of the subnetwork, we propose that TCF3 was a potential key regulator in this regulatory network. In conclusion, this is the first study perform on global expression profiling of miRNAs and TFs relating to AML. These results may enhance our understanding of the molecular mechanisms underlying AML and provide potential targets for future therapeutics.
authors.affiliation: Institute of Biochemistry and Molecular Biology, Guangdong Medical University, Zhanjiang, Guangdong 524023, P.R. China.
authors.forename: Xiao-Cong
authors.initials: XC
authors.lastname: Lin
authors.affiliation: Shenzhen Pingshan People's Hospital, Shenzhen, Guangdong 518118, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Shenzhen Pingshan People's Hospital, Shenzhen, Guangdong 518118, P.R. China.
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Sun
authors.affiliation: Clinical Medical Research Center, Shenzhen People's Hospital, Shenzhen, Guangdong 518020, P.R. China.
authors.forename: Jin-Li
authors.initials: JL
authors.lastname: Wen
authors.affiliation: Department of Hematology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Hematology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Zhang
authors.affiliation: Department of Hematology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Yang
authors.affiliation: Institute of Biochemistry and Molecular Biology, Guangdong Medical University, Zhanjiang, Guangdong 524023, P.R. China.
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Zhang
authors.affiliation: Clinical Medical Research Center, Shenzhen People's Hospital, Shenzhen, Guangdong 518020, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Dai
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D053263:Gene Regulatory Networks; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D035683:MicroRNAs; D014157:Transcription Factors