title: 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.
authors.affiliation: Department of Pediatric Oncology and Hematology, Erasmus MC/Sophia Children's Hospital, University Medical Centre Rotterdam, Rotterdam, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Akbari Moqadam
authors.forename: E A M
authors.initials: EA
authors.lastname: Lange-Turenhout
authors.forename: I M
authors.initials: IM
authors.lastname: Ariës
authors.forename: R
authors.initials: R
authors.lastname: Pieters
authors.forename: M L
authors.initials: ML
authors.lastname: den Boer
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015870:Gene Expression; D015973:Gene Expression Regulation, Leukemic; D023061:Gene Order; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics*; D014750:Vincristine / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C544266:MIRN100 microRNA, human; C531888:MIRN125 microRNA, human; C561679:MIRN99 microRNA, human; D035683:MicroRNAs; D014750:Vincristine
keywords: Leukemia; Vincristine resistance; miR-100; miR-125b; miR-99a; miRNA