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Acute Leukemias

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.

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Acknowledgements

This work was financially supported by the Netherlands Organization for Scientific Research (NWO-Vidi Grant, MLdB), the Quality of Life Foundation (MLdB/RP) and the Pediatric Oncology Foundation Rotterdam, KOCR (MLdB/RP).

Author contributions

FAM performed research, analyzed data and wrote the manuscript; JMB preformed the miRNA-mRNA expression data integration, analyzed the data and revised the manuscript; EAML-T performed research, analyzed data and revised the manuscript; RP and MLdB supervised research, analyzed data, wrote and revised the manuscript. All authors approved the final version of the manuscript.

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Correspondence to M L den Boer.

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Akbari Moqadam, F., Boer, J., Lange-Turenhout, E. et al. Altered expression of miR-24, miR-126 and miR-365 does not affect viability of childhood TCF3-rearranged leukemia cells. Leukemia 28, 1008–1014 (2014). https://doi.org/10.1038/leu.2013.308

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