Abstract
MiR-424 plays an important role via promoting the monocytic differentiation in many human leukemia cell lines. Here, we report that miR-424 decreased miR-125b expression to 36 % by directly targeting caudal type homeobox 2. However, miR-424 also decreased expression of Fes, PU.1 and colony-stimulating factor receptor (MCSFR). As Fes, PU.1 and MCSFR were down-regulated by over-expression of miR-125b (unpublished work), a similar effect of miR-424 and Fes siRNA on CD64, Egr-1, Egr-2 and CEBPA indicates that Fes may be an important downstream target of miR-424. We hypothesize that miR-424 promotes monocytic differentiation by regulating other critical factors and miR-424 has high affinity for these factors. For the first time, the molecular mechanism of miR-424 during monocytic differentiation of U937 cells has been elucidated in this study.
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References
Bousquet M, Quelen C, Rosati R et al (2008) Myeloid cell differentiation arrest by miR-125b-1 in myelodysplastic syndrome and acute myeloid leukemia with the t(2;11)(p21;q23) translocation. J Exp Med 205:2499–2506
Bousquet M, Harris MH, Zhou B, Lodish HF (2010) MicroRNA miR-125b causes leukemia. Proc Natl Acad Sci USA 107:21558–21563
Faraoni I, Laterza S, Ardiri D, Ciardi C, Fazi F, Lo-Coco F (2012) MiR-424 and miR-155 deregulated expression in cytogenetically normal acute myeloid leukaemia: correlation with NPM1 and FLT3 mutation status. J Hematol Oncol 5:26–30
Forrest ARR, Kanamori-Katayama M, Tomaru Y et al (2010) Induction of microRNAs mir-155, mir-222, mir-424 and mir-503, promotes monocytic differentiation through combinatorial regulation. Leukemia 24:460–466
Gefen N, Binder V, Zaliova M, Linka Y, Morrow M, Novosel A, Edry L, Hertzberg L, Shomron N, Williams O, Trka J, Borkhardt A, Izraeli S (2010) Hsa-mir-125b-2 is highly expressed in childhood ETV6/RUNX1 (TEL/AML1) leukemias and confers survival advantage to growth inhibitory signals independent of p53. Leukemia 24:89–96
Kasashima K, Nakamura Y, Kozu T (2004) Altered expression profiles of microRNAs during TPA-induced differentiation of HL-60 cells. Biochem Biophys Res Commun 322:403–410
Kuckenberg P, Buhl S, Woynecki T, Furden BV, Tolkunova E, Seiffe F, Moser M, Tomilin A, Winterhager E, Schorle H (2010) The transcription factor TCFAP2C/AP-2γ cooperates with CDX2 to maintain trophectoderm formation. Mol Cell Biol 30:3310–3320
Lin KY, Zhang XJ, Feng DD, Zhang H, Zeng CW, Han BW, Zhou AD, Qu LH, Xu L, Chen YQ (2011) miR-125b, a target of CDX2, regulates cell differentiation through repression of the core binding factor in hematopoietic malignancies. J Biol Chem 286:38253–38263
Marcucci G, Maharry K, Wu YZ et al (2010) IDH1 and IDH2 gene mutations identify novel molecular subsets within de novo cytogenetically normal acute myeloid leukemia: a cancer and leukemia group B study. J Clin Oncol 28:2348–2355
Rahimian A, Soleimani M, Kaviani S, Aghaee-Bakhtiari SH, Atashi A, Arefian E, Nikougoftar M (2011) Bypassing the maturation arrest in myeloid cell line U937 by over-expression of microRNA-424. Hematology 16:298–302
Rawat VPS, Thoene S, Naidu VM et al (2008) Overexpression of CDX2 perturbs HOX gene expression in murine progenitors depending on its N-terminal domain and is closely correlated with deregulated HOX gene expression in human acute myeloid leukemia. Blood 111:309–319
Riedt T, Ebinger M, Salih HR, Tomiuk J, Handgretinger R, Kanz L, Grünebach F, Lengerke C (2009) Aberrant expression of the homeobox gene CDX2 in pediatric acute lymphoblastic leukemia. Blood 113:4049–4051
Rosa A, Ballarino M, Sorrentino A, Sthandier O, De Angelis FG, Marchioni M, Masella B, Guarini A, Fatica A, Peschle C, Bozzoni I (2007) The interplay between the master transcription factor PU.1 and miR-424 regulates human monocyte/macrophage differentiation. Proc Natl Acad Sci USA 104:19849–19854
Scholl C, Bansal D, Döhner K, Eiwen K, Huntly BJP, Lee BH, Rücker FG, Schlenk RF, Bullinger L, Döhner H, Gilliland DG, Fröhling S (2007) The homeobox gene CDX2 is aberrantly expressed in most cases of acute myeloid leukemia and promotes leukemogenesis. J Clin Invest 117:1037–1048
Schotte D, Pieters R, Den Boer ML (2012) MicroRNAs in acute leukemia: from biological players to clinical contributors. Leukemia 26:1–12
Thoene S, Rawat VPS, Heilmeier B, Hoster E, Metzeler KH, Herold T, Hiddemann W, Gokbuget N, Hoelzer D, Bohlander SK, Feuring-Buske M, Buske C (2009) The homeobox gene CDX2 is aberrantly expressed and associated with an inferior prognosis in patients with acute lymphoblastic leukemia. Leukemia 23:649–655
Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, Harris NL, Le Beau MM, Hellström-Lindberg E, Tefferi A, Bloomfield CD (2009) The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 114:937–951
Zeng CW, Zhang XJ, Lin KY, Ye H, Feng SY, Zhang H, Chen YQ (2012) Camptothecin induces apoptosis in cancer cells via microRNA-125b-mediated mitochondrial pathways. Mol Pharmacol 81:578–586
Zhang YJ, Gao JS, Tang XL, Tucker LD, Quesenberry P, Rigoutsos I, Ramratnam B (2009) MicroRNA 125a and its regulation of the p53 tumor suppressor gene. FEBS Lett 583:3725–3730
Acknowledgments
We thank Prof. Qinglong Guo for providing the cell lines used in this study, M.D. Xuepeng Deng and M.D. Jiajie Tu for helpful comments on the manuscript and the members of the Tao Xi lab for helpful discussion.
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Shen, X., Tang, J., Hu, J. et al. MiR-424 regulates monocytic differentiation of human leukemia U937 cells by directly targeting CDX2. Biotechnol Lett 35, 1799–1806 (2013). https://doi.org/10.1007/s10529-013-1264-9
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DOI: https://doi.org/10.1007/s10529-013-1264-9