Decreased expression of microRNA-122 is associated with an unfavorable prognosis in childhood acute myeloid leukemia and function analysis indicates a therapeutic potential

Pathol Res Pract. 2017 Sep;213(9):1166-1172. doi: 10.1016/j.prp.2017.06.017. Epub 2017 Jun 28.

Abstract

MicroRNA (miR)-122 functions as a tumor suppressor in various human cancers. However, its involvement in childhood acute myeloid leukemia (AML) remains unknown. In this study, quantitative real-time PCR assay demonstrated that miR-122 expression in bone marrow specimens from AML children were significantly lower than that in non-malignant controls (P<0.001). Statistically, AML children with low miR-122 expression more frequently had large white blood cell count (P=0.022), French-American-British classification subtype M7 (P<0.001), unfavorable cytogenetics (P=0.002) and day 7 response to the treatment (P=0.036), short relapse-free (P=0.001) and overall (P=0.008) survivals than those with high expression. Multivariate analysis also determined that miR-122 expression was an independent prognostic factor for both relapse-free and overall survivals. Functionally, the enforced expression of miR-122 in AML cell lines efficiently suppressed cell proliferation and reduced the ratio of S-phase cells in vitro (all P<0.05). In conclusion, the abnormal expression of miR-122 may be a marker of the aggressive progression in childhood AML. Importantly, its downregulation may serve as a prognostic factor to predict poor outcome. Our study also reveal that miR-122 may function as a tumor suppressor in childhood AML, highlighting a new therapeutic strategy for this malignancy.

Keywords: Cell proliferation; Childhood acute myeloid leukemia; Prognosis; Tumor suppressor; microRNA-122.

MeSH terms

  • Adolescent
  • Biomarkers, Tumor / genetics*
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Female
  • Genes, Tumor Suppressor
  • Humans
  • Kaplan-Meier Estimate
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / mortality
  • Male
  • MicroRNAs / analysis
  • MicroRNAs / biosynthesis*
  • Prognosis
  • Proportional Hazards Models

Substances

  • Biomarkers, Tumor
  • MIRN122 microRNA, human
  • MicroRNAs