Pituitary tumor transforming gene 1 promotes proliferation and malignant phenotype in osteosarcoma via NF-KB signaling

Background: Pituitary tumor transforming gene (PTTG) is an oncogene reported to be actively promotes tumorigenesis in multiple tumors. Osteosarcoma (OS) is the most common primary osseous sarcoma, however, the functional significance and mechanisms underlying whether and how PTTG1 promotes OS remain largely unknown. Methods: Here, in our study, PTTG1 levels in clinical samples and cell lines were determined by western blotting and immunohistochemistry. The viability and migratory/invasive potential of OS cells were assessed using Cell Counting Kit-8, colony formation, wound healing, and Transwell assays. The effects of PTTG1 on NF-KB signaling pathways were evaluated both in vivo and in vitro. Results: An abnormally elevated expression of PTTG1was confirmed in human OS tissues and OS cell lines and PTTG1 levels were positively correlated with OS clinicopathological grade. We further showed that knocking down PTTG1 attenuated the viability and migratory/invasive capacity of OS cells (MG63 and HOS-8603). Additionally, the following key mechanistic principle was revealed: knockdown PTTG1-mediated OS tumorgenesis supression was associated with inactivation of the NF-KB pathway. We confirmed these results by additional nonpharmacological intervention and same conclusions were obtained in the context of opposite functional analyses. Furthermore, we also demonstrated that OS cell lines overexpressed PTTG1 showed increased tumorigenesis in athymic nude mice. Conclusions: To sum up, the present study suggests that PTTG1 is involved in the enhancement of the malignancy and carcinogenesis of OS by regulating NF-KB signaling. Accordingly, PTTG1 likely functions as an oncogene in OS and may represent a potential therapeutic target for this cancer. (c) 2022 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.