MiR-146a affects the alteration in myeloid differentiation induced by hydroquinone in human CD34 super(+) hematopoietic progenitor cells and HL-60 cells

The MiR-146a/TRAF6/NF- Kappa B axis is important for the regulation of hematopoiesis and the immune system. To identify the key axis that regulates benzene-induced hematotoxicity or even leukemia, we investigated miR-146a expression in human CD34 super(+) hematopoietic progenitor cells (HPCs) and hu...

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Veröffentlicht in:Toxicology research (Cambridge) 2016-05, Vol.5 (3), p.848-858
Hauptverfasser: Yuan, Weixin, Sun, Qing, Jiang, Yanping, Zhang, Xinjie, Chen, Liping, Xie, Chunjiao, Qin, Fei, Chen, Yuncong, Lv, Hongxin, Chen, Wen, Xiao, Yongmei
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Sprache:eng
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Zusammenfassung:The MiR-146a/TRAF6/NF- Kappa B axis is important for the regulation of hematopoiesis and the immune system. To identify the key axis that regulates benzene-induced hematotoxicity or even leukemia, we investigated miR-146a expression in human CD34 super(+) hematopoietic progenitor cells (HPCs) and human acute promyelocytic leukemia cells (HL-60) during the differentiation process. By performing a colony formation assay and flow cytometry on cells in the differentiation process after hydroquinone treatment, we found that hydroquinone induced a marked reduction of differentiation toward myeloid cells and immune cells in CD34 super(+) cells (5 days exposure) as well as in HL-60 cells (3 h exposure). Further study using real-time PCR and western blot showed that the impaired myeloid differentiation was accompanied by the up-regulation of miR-146a and the down-regulation of TRAF6 and NF- Kappa B. Using the miR-146a-5p inhibitor to suppress miR-146a expression could relieve the inhibitory effect on myeloid differentiation induced by hydroquinone to a certain extent. At the same time, the level of TRAF6 protein, as well as the phosphorylated I Kappa B alpha protein which indicates NF- Kappa B transcriptional activity was restored to the same levels as the control group. These results suggested that hydroquinone induced a dysregulation of miR-146a and its downstream NF- Kappa B transcriptional factor pathway, which might be an early event in the generation of benzene-induced differentiation disturbance and subsequent leukemogenesis.
ISSN:2045-452X
2045-4538
DOI:10.1039/c5tx00419e