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

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.