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Cancer Cell International

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01-12-2020 | Chloroquin | Primary research

Aurora-B knockdown inhibits osteosarcoma metastasis by inducing autophagy via the mTOR/ULK1 pathway

Authors: Xin Wu, Jia-ming Liu, Hong-hai Song, Qi-kun Yang, Hui Ying, Wei-lai Tong, Yang Zhou, Zhi-li Liu

Published in: Cancer Cell International | Issue 1/2020

Abstract

Background

Autophagy plays an essential role in metastasis of malignancies. Although our studies showed that Aurora-B facilitate pulmonary metastasis in OS, the mechanism of Aurora-B kinase on autophagy and metastasis in OS has not been explored.

Methods

Clinical-pathological parameters and follow-up information was collected in OS patients. Immunohistochemical staining was performed to detect Aurora-B and LC3 protein in OS tissues. Short hairpin RNA transfection was used to silence Aurora-B in OS cells. Real-time quantitative PCR (RT-qPCR) was performed to detect Aurora-B mRNA expression in OS cells. Aurora-B and autophagy related protein were measured by Western blot. Transmission electron microscopy and laser scanning confocal microscopy were performed to observe the formation of autophagosomes and autolysosomes. Migratory and invasive ability of OS cells were measured by Wound healing and transwell assays. Orthotopic xenograft model was used to evaluate the effect of autophagy mediated by Aurora-B inhibition on pulmonary metastasis of OS.

Results

The elevated expression of Aurora-B protein in OS tissues negatively associated with the overall survival of OS patients. Further investigation has found that Aurora-B expression was negatively correlative with autophagy related protein LC3 in OS patient tissues. Knockdown Aurora-B stimulates autophagy and inhibits migratory and invasive ability of OS cells. Mechanistically, Aurora-B knockdown suppressed the mTOR/ULK1 signaling pathway and reactivation of the mTOR/ULK1 pathway decreased autophagy level. Furthermore, the inhibition effect of silencing Aurora-B on migration and invasion of OS was reversed by chloroquine and mTOR activator in vitro and vivo.

Conclusions

Our results suggest that silencing of Aurora-B stimulate autophagy via decreasing mTOR/ULK1 and result in inhibiting OS metastasis. Targeted Aurora-B/mTOR/ULK1 pathway may be a promising treatment strategy for OS patients.

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Title: Aurora-B knockdown inhibits osteosarcoma metastasis by inducing autophagy via the mTOR/ULK1 pathway
Authors: Xin Wu
Jia-ming Liu
Hong-hai Song
Qi-kun Yang
Hui Ying
Wei-lai Tong
Yang Zhou
Zhi-li Liu
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Chloroquin
osteosarcoma
Metastasis
Chloroquin
Osteosarcoma
Published in: Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI: https://doi.org/10.1186/s12935-020-01674-1

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Abstract

Background

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Conclusions

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