miR-34a induces neutrophil apoptosis by regulating Cdc42-WASP-Arp2/3 pathway-mediated F-actin remodeling and ROS production

Background The number of neutrophils is significantly reduced in myelodysplastic syndrome (MDS), but the molecular basis remains unclear. We recently found that miR-34a was significantly increased in MDS neutrophils. Therefore, this study aims to clarify the effects of aberrant miR-34a expression on...

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Main Authors: Meiwan Cao (Author), Baoling Peng (Author), Huan Chen (Author), Min Yang (Author), Peiyu Chen (Author), Liping Ye (Author), Hongli Wang (Author), Lu Ren (Author), Jing Xie (Author), Jingnan Zhu (Author), Xiangye Xu (Author), Wanfu Xu (Author), Lanlan Geng (Author), Sitang Gong (Author)
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Published: Taylor & Francis Group, 2022-12-01T00:00:00Z.
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042 |a dc 
100 1 0 |a Meiwan Cao  |e author 
700 1 0 |a Baoling Peng  |e author 
700 1 0 |a Huan Chen  |e author 
700 1 0 |a Min Yang  |e author 
700 1 0 |a Peiyu Chen  |e author 
700 1 0 |a Liping Ye  |e author 
700 1 0 |a Hongli Wang  |e author 
700 1 0 |a Lu Ren  |e author 
700 1 0 |a Jing Xie  |e author 
700 1 0 |a Jingnan Zhu  |e author 
700 1 0 |a Xiangye Xu  |e author 
700 1 0 |a Wanfu Xu  |e author 
700 1 0 |a Lanlan Geng  |e author 
700 1 0 |a Sitang Gong  |e author 
245 0 0 |a miR-34a induces neutrophil apoptosis by regulating Cdc42-WASP-Arp2/3 pathway-mediated F-actin remodeling and ROS production 
260 |b Taylor & Francis Group,   |c 2022-12-01T00:00:00Z. 
500 |a 10.1080/13510002.2022.2102843 
500 |a 1743-2928 
500 |a 1351-0002 
520 |a Background The number of neutrophils is significantly reduced in myelodysplastic syndrome (MDS), but the molecular basis remains unclear. We recently found that miR-34a was significantly increased in MDS neutrophils. Therefore, this study aims to clarify the effects of aberrant miR-34a expression on neutrophil counts.Methods miR-34a mimics/inhibitor transfection were performed in neutrophil-like differentiated HL60 (dHL60) cells, and a FACSCalibur flow cytometer was used to measure ROS production and apoptosis. In addition, the Cdc42-WASP-Arp2/3 pathway inhibitor (ML141) and activator (CN02) treated the dHL60 cells, and then ROS production, apoptosis and related proteins expression were detected. And, luciferase reporter assay to verify the relationship of miR-34a and the Cdc42-WASP-Arp2/3 pathway.Results overexpression of miR-34a could induce ROS production and apoptosis, decrease the expression levels of DOCK8, p-WASP, WASP, Arp2, Arp3, and increase F-actin's expression. Meanwhile, knockdown of miR-34a could decrease ROS production and apoptosis, increase the expression of DOCK8, p-WASP, WASP, Arp2, Arp3, and decrease F-actin's expression. Immunofluorescence staining showed aberrant miR-34a and Cdc42-WASP-Arp2/3 pathway could induce F-actin membrane transfer. Luciferase reporter assay indicated that DOCK8 was a direct target gene of miR-34a.Conclusion These data indicates miR-34a may induce neutrophil apoptosis by regulating Cdc42-WASP-Arp2/3 pathway-mediated F-actin remodeling and ROS production. 
546 |a EN 
690 |a MiR-34a 
690 |a myelodysplastic syndromes 
690 |a neutrophils 
690 |a apoptosis 
690 |a ROS 
690 |a F-actin 
690 |a Pathology 
690 |a RB1-214 
690 |a Biology (General) 
690 |a QH301-705.5 
655 7 |a article  |2 local 
786 0 |n Redox Report, Vol 27, Iss 1, Pp 167-175 (2022) 
787 0 |n https://www.tandfonline.com/doi/10.1080/13510002.2022.2102843 
787 0 |n https://doaj.org/toc/1351-0002 
787 0 |n https://doaj.org/toc/1743-2928 
856 4 1 |u https://doaj.org/article/e4faff7aa9bc455c9f1f62c7839a3b40  |z Connect to this object online.