Aurora-B knockdown inhibits osteosarcoma metastasis by inducing autophagy via the mTOR/ULK1 pathway
- PDF / 4,351,283 Bytes
- 14 Pages / 595.276 x 790.866 pts Page_size
- 9 Downloads / 195 Views
PRIMARY RESEARCH
Cancer Cell International Open Access
Aurora‑B knockdown inhibits osteosarcoma metastasis by inducing autophagy via the mTOR/ULK1 pathway Xin Wu1,2†, Jia‑ming Liu1,2†, Hong‑hai Song1,2, Qi‑kun Yang1, Hui Ying1, Wei‑lai Tong1,2, Yang Zhou1 and Zhi‑li Liu1,2*
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. Immunohisto‑ chemical 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 pul‑ monary 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. Keywords: Osteosarcoma, Aurora-B, The mTOR/ULK1 pathway, Autophagy, Metastasis
*Correspondence: [email protected] † Xin Wu and Jia-ming Liu contributed equally to this work 1 Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University, No.17 Yong Wai Zheng Street, Donghu District, Nanchang, Jiangxi 330006, People’s Republic of China Full list of author information is available at the end of the article
Background Osteosarcoma (OS), a highly aggressive tumor with a tendency to metastasize to the lung, is the most common malignant bone tumor in children and adolescents [1, 2], and metastasis to the lung is the leading cause of death in patients with OS [3]. Despite the combination of surgery resection with neoadjuvant chemotherapy
© The Author(s) 2020. This article is
Data Loading...
