MicroRNA biomarker identification for pediatric acute myeloid leukemia based on a novel bioinformatics model

Oncotarget. 2015 Sep 22;6(28):26424-36. doi: 10.18632/oncotarget.4459.

Abstract

Acute myeloid leukemia (AML) in children is a complex and heterogeneous disease. The identification of reliable and stable molecular biomarkers for diagnosis, especially early diagnosis, remains a significant therapeutic challenge. Aberrant microRNA expression could be used for cancer diagnosis and treatment selection. Here, we describe a novel bioinformatics model for the prediction of microRNA biomarkers for the diagnosis of paediatric AML based on computational functional analysis of the microRNA regulatory network substructure. microRNA-196b, microRNA-155 and microRNA-25 were identified as putative diagnostic biomarkers for pediatric AML. Further systematic analysis confirmed the association of the predicted microRNAs with the leukemogenesis of AML. In vitro q-PCR experiments showed that microRNA-155 is significantly overexpressed in children with AML and microRNA-196b is significantly overexpressed in subgroups M4-M5 of the French-American-British classification system. These results suggest that microRNA-155 is a potential diagnostic biomarker for all subgroups of paediatric AML, whereas microRNA-196b is specific for subgroups M4-M5.

Keywords: bioinformatics model; microRNA biomarkers; microRNA regulatory network; pediatric acute myeloid leukemia; transcription factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age of Onset
  • Biomarkers, Tumor / genetics*
  • Child
  • Child, Preschool
  • Computational Biology*
  • Databases, Genetic
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Infant
  • Infant, Newborn
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / epidemiology
  • Leukemia, Myeloid, Acute / genetics*
  • MicroRNAs / genetics*
  • Phenotype
  • Reproducibility of Results
  • Transcription, Genetic

Substances

  • Biomarkers, Tumor
  • MIRN155 microRNA, human
  • MIRN196 microRNA, human
  • MicroRNAs