title: Altered expression of miR-24, miR-126 and miR-365 does not affect viability of childhood TCF3-rearranged leukemia cells.
abstract: Among the microRNAs (miRNAs) that control different cellular processes, miR-24, miR-126 and miR-365 were shown to regulate cell cycle progression and apoptosis in various types of tumors. Interestingly, these three miRNAs were downregulated in pediatric TCF3-rearranged B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Here, we showed that individual or combined overexpression of miR-24, miR-126 and miR-365 can neither alter the cell cycle progression nor the amount of apoptosis in 697, KASUMI-2 or MHH-CALL-3 TCF3-rearranged leukemic cells. We further integrated the miRNA-mRNA expression data of 37 children with BCP-ALL to identify candidate target genes for these three miRNAs. However, the expression levels of selected candidate target genes (ELL, EBF3 and IRF4 for miR-24, PITPNC1 for miR-126 and ZAP-70 for miR-365) did not reduce upon miRNAs overexpression in MHH-CALL-3 TCF3-rearranged leukemic cells. Although the expression level of AURKB-a validated target for miR-24-was reduced upon miR-24 overexpression in hepatocarcinoma HEP-G2 cells, overexpression of miR-24 cannot alter AURKB expression levels in MHH-CALL-3 TCF3-rearranged leukemic cells. Taken together, our data suggest that miRNAs' function is highly tissue-dependent and that a defined biological target gene or function of one miRNA in a specific tissue cannot be extended as a generalized target/function for that miRNA in all types of cells/tissues.
authors.affiliation: Department of Pediatric Oncology and Hematology, Erasmus MC/Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Akbari Moqadam
authors.affiliation: Department of Pediatric Oncology and Hematology, Erasmus MC/Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: J M
authors.initials: JM
authors.lastname: Boer
authors.affiliation: Department of Pediatric Oncology and Hematology, Erasmus MC/Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: E A M
authors.initials: EA
authors.lastname: Lange-Turenhout
authors.affiliation: Department of Pediatric Oncology and Hematology, Erasmus MC/Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Pieters
authors.affiliation: Department of Pediatric Oncology and Hematology, Erasmus MC/Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: M L
authors.initials: ML
authors.lastname: den Boer
mesh_terms: D017209:Apoptosis; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D017931:DNA Primers; D015321:Gene Rearrangement; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D035683:MicroRNAs; C407909:TCF3 protein, human