MiR-125b, miR-100 and miR-99a co-regulate vincristine resistance in childhood acute lymphoblastic leukemia

Leuk Res. 2013 Oct;37(10):1315-21. doi: 10.1016/j.leukres.2013.06.027. Epub 2013 Jul 31.

Abstract

MicroRNA-125b (miR-125b), miR-99a and miR-100 are overexpressed in vincristine-resistant acute lymphoblastic leukemia (ALL). Cellular viability of ETV6-RUNX1-positive Reh cells significantly increased in presence of 9 ng/mL vincristine upon co-expression of miR-125b/miR-99a (91 ± 4%), miR-125b/miR-100 (93 ± 5%) or miR-125b/miR-99a/miR-100 (82 ± 17%) compared with miR-125b-transduced cells (38 ± 13%, P<0.05). Co-expression of these miRNAs resulted in downregulation of DNTT, NUCKS1, MALAT1, SNRPE, PNO1, SET, KIF5B, PRPS2, RPS11, RPL38 and RPL23A (fold-change 1.3-1.9, p<0.05). Similarly, 7 out of these genes are lower expressed in vincristine-resistant ALL cells of children (p<0.05). The concerted function of miR-125b in combination with miR-99a and/or miR-100 illustrates the complexity of vincristine-resistant pediatric ALL.

Keywords: Leukemia; Vincristine resistance; miR-100; miR-125b; miR-99a; miRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Base Sequence
  • Child
  • Child, Preschool
  • Drug Resistance, Neoplasm / genetics*
  • Gene Expression
  • Gene Expression Regulation, Leukemic
  • Gene Order
  • Humans
  • MicroRNAs / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Vincristine / pharmacology*
  • Vincristine / therapeutic use

Substances

  • Antineoplastic Agents, Phytogenic
  • MIRN100 microRNA, human
  • MIRN125 microRNA, human
  • MIRN99 microRNA, human
  • MicroRNAs
  • Vincristine