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Aurora-B Promotes Osteosarcoma Cell Growth and Metastasis Through Activation of the NPM1/ERK/NF-κβ/MMPs Axis

Authors Song H, Zhou Y, Peng A, Liu J, Wu X, Chen W, Liu Z

Received 7 March 2020

Accepted for publication 10 May 2020

Published 23 June 2020 Volume 2020:12 Pages 4817—4827

DOI https://doi.org/10.2147/CMAR.S252847

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Eileen O'Reilly


Honghai Song,1,2,* Yang Zhou,1,* Aifen Peng,3 Jiaming Liu,1,2,4 Xin Wu,1 Wenzhao Chen,1 Zhili Liu1,2,5

1Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang 330006, People’s Republic of China; 2Institute of Spinal and Spinal Cord Diseases, Nanchang University, Nanchang 330031, People’s Republic of China; 3College of Humanities, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330004, People’s Republic of China; 4Jiangxi Institute of Respiratory Disease, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, People’s Republic of China; 5Division of Science and Technology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Zhili Liu
Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, People’s Republic of China
Tel/ Fax +86-79188693201
Email zgm7977@163.com

Purpose: Osteosarcoma (OS) is the most common primary malignant tumor of the bone in young adolescents and children. We explored the underlying mechanism of Aurora-B in promoting OS cell proliferation and metastasis.
Patient and Methods: Bioinformatics was employed to predict the substrate of Aurora-B. IHC and Western blot were used to confirm the correlation between Aurora-B and NPM1. ERK/NF-κβ pathway-related proteins were detected by Western blot and immunofluorescence (IF). CCK8, wound healing, transwell, and Tunel assays were used to identify the cell proliferation, migration and apoptosis potential. Spontaneous metastasis xenografts were established to confirm the role of Aurora-B and NPM1.
Results: Aurora-B promotes NPM1 phosphorylation on Ser125. The phosphorylation of NPM1Ser125 induced by Aurora-B activates the ERK/NF-κβ signaling. Further study revealed that Aurora-B promotes proliferation, migration and inhibits apoptosis via phosphorylating NPM1 in vitro and in vivo.
Conclusion: Aurora-B promotes OS malignancy via phosphorylating NPM1Ser125 and activating ERK/NF-κβ signaling.

Keywords: Aurora-B, osteosarcoma, NPM1, ERK, NF-κβ

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