Molecular dysfunctions in acute myeloid leukemia revealed by integrated analysis of microRNA and transcription factor

  • Authors:
    • Xiao-Cong Lin
    • Yong Xu
    • Guo-Ping Sun
    • Jin-Li Wen
    • Ning Li
    • Yu-Ming Zhang
    • Zhi-Gang Yang
    • Hai-Tao Zhang
    • Yong Dai
  • View Affiliations

  • Published online on: April 15, 2016     https://doi.org/10.3892/ijo.2016.3489
  • Pages: 2367-2380
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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.
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June-2016
Volume 48 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Lin X, Xu Y, Sun G, Wen J, Li N, Zhang Y, Yang Z, Zhang H and Dai Y: Molecular dysfunctions in acute myeloid leukemia revealed by integrated analysis of microRNA and transcription factor. Int J Oncol 48: 2367-2380, 2016.
APA
Lin, X., Xu, Y., Sun, G., Wen, J., Li, N., Zhang, Y. ... Dai, Y. (2016). Molecular dysfunctions in acute myeloid leukemia revealed by integrated analysis of microRNA and transcription factor. International Journal of Oncology, 48, 2367-2380. https://doi.org/10.3892/ijo.2016.3489
MLA
Lin, X., Xu, Y., Sun, G., Wen, J., Li, N., Zhang, Y., Yang, Z., Zhang, H., Dai, Y."Molecular dysfunctions in acute myeloid leukemia revealed by integrated analysis of microRNA and transcription factor". International Journal of Oncology 48.6 (2016): 2367-2380.
Chicago
Lin, X., Xu, Y., Sun, G., Wen, J., Li, N., Zhang, Y., Yang, Z., Zhang, H., Dai, Y."Molecular dysfunctions in acute myeloid leukemia revealed by integrated analysis of microRNA and transcription factor". International Journal of Oncology 48, no. 6 (2016): 2367-2380. https://doi.org/10.3892/ijo.2016.3489