The oncogenic role of GNL3 in the progression and metastasis of osteosarcoma

• Main Authors: Li TY, Li L, Wu XY, Tian KX, Wang YZ
• Format: Article
• Language: English
• Published: Dove Medical Press 2019-03-01
• Series: Cancer Management and Research
• Subjects: G protein nucleolar 3; GNL3; osteosarcoma; EMT; XBP1
• Online Access: https://www.dovepress.com/the-oncogenic-role-of-gnl3-in-the-progression-and-metastasis-of-osteos-peer-reviewed-article-CMAR

Tianyou Li, Long Li, Xiangyu Wu, Kaixuan Tian, Yanzhou Wang Department of Pediatric Orthopedics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China Background: GNL3 has been reported to be up-regulated in cancers and function in tumor progression, whereas the role of GNL3 in the progression of osteosarcoma remains unclear. Materials and methods: In this study, we blocked the expression of GNL3 by siRNA interference in osteosarcoma cell lines MG63 and U20S. CCK8, colony formation, wound-healing, Transwell, flow cytometry, and Hoechst/PI staining assays were used to examine the effects of GNL3 knockdown on cell proliferation, migration, invasion and apoptosis in MG63 and U20S cells. The relative activity of MMP9 was detected using Gelatin zymography assay. Western blot was performed to detect the expression of related proteins. Results: We found that silencing of GNL3 reduced the growth, migration, and invasion abilities of MG63 and U20S cells. Moreover, silencing GNL3 triggered cell cycle arrest in MG63 and U20S cells, as well as promoted cell apoptosis. In addition, depletion of GNL3 was observed to reduce the activity of MMP9 and suppress the process of epithelial–mesenchymal transition (EMT) through up-regulation of E-cadherin and down-regulation of N-cadherin. Furthermore, we found that X-box-binding protein 1 (XBP1) could bind to GNL3 using dual-luciferase reporter assay, and XBP1 overexpression could restore the inhibitory effects on proliferation, invasion, and EMT in MG63 and U20S cells caused by GNL3 knockdown. Conclusion: These data suggest that GNL3 functions as an oncogene in the progression of osteosarcoma by regulation of EMT, and XBP1 is also involved in its mechanism. Keywords: G protein nucleolar 3, GNL3, osteosarcoma, EMT, XBP1