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Mol Immunol. 2019 Jun 5;112:206-214. doi: 10.1016/j.molimm.2019.06.001. [Epub ahead of print]

Inducible overexpression of zebrafish microRNA-722 suppresses chemotaxis of human neutrophil like cells.

Author information

1
Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
2
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Collaborative Core for Cancer Bioinformatics, Indiana University Simon Cancer Center, Indianapolis, IN 46202, USA.
3
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Collaborative Core for Cancer Bioinformatics, Indiana University Simon Cancer Center, Indianapolis, IN 46202, USA; Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
4
Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA; Purdue Institute for Inflammation, Immunology, & Infectious Disease, Purdue University, West Lafayette, IN 47907, USA; Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA. Electronic address: qingdeng@purdue.edu.

Abstract

Neutrophil migration is essential for battling against infections but also drives chronic inflammation. Since primary neutrophils are terminally differentiated and not genetically tractable, leukemia cells such as HL-60 are differentiated into neutrophil-like cells to study mechanisms underlying neutrophil migration. However, constitutive overexpression or inhibition in this cell line does not allow the characterization of the genes that affect the differentiation process. Here we apply the tet-on system to induce the expression of a zebrafish microRNA, dre-miR-722, in differentiated HL-60. Overexpression of miR-722 reduced the mRNA level of genes in the chemotaxis and inflammation pathways, including Ras-Related C3 Botulinum Toxin Substrate 2 (RAC2). Consistently, polarization of the actin cytoskeleton, cell migration and generation of the reactive oxygen species are significantly inhibited upon induced miR-722 overexpression. Together, zebrafish miR-722 is a suppressor for migration and signaling in human neutrophil like cells.

KEYWORDS:

Chemotaxis; HL-60; Inducible expression; RAC2; Signaling; microRNA

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