Osteosarcoma (OS), also known as osteogenic sarcoma, is a malignant tumor originating from the mesenchymal tissue. It is one of the most common and invasive primary malignant bone tumors that frequently occurs in children and adolescents, with more prevalence in male patients than that in female ones and an incidence of greater than 4 per million [[1], [2], [3], [4]]. The appearance of OS is closely related to the peak period of growth of the long diaphysis, mainly arising in the metaphyseal ends of the long bones [5,6]. According to histological characteristics, OS usually has a high degree of malignancy, which mainly manifests as metastasis [7,8]. With the potential for local invasion and metastasis to other parts of the body, the lungs are the most common site of metastasis [9]. Approximately 20% of OS patients have pulmonary metastasis at initial diagnosis, and approximately 40% of non-metastatic OS patients develop pulmonary metastasis in the later stages of the disease [10]. With invasion and metastasis, malignant OS cells spread to multiple organs of the body, making radical treatment very challenging. Therefore, there is an urgent need to better understand the molecular mechanisms underlying the pathogenesis of this aggressive malignancy.

The pituitary tumor-transforming gene (PTTG) family contains at least three homologous proteins, PTTG1, PTTG2, and PTTG3, among which PTTG1 has been studied in the most detail [[11], [12], [13]]. PTTG1 was first identified as a proto-oncogene in the rodent pituitary tumor cell line GH4 [14]. The human PTTG1 gene is located on chromosome 5q33 and encodes a protein composed of 203 amino acids [15]. Several studies have shown that PTTG1 is a multifunctional protein that plays an important role in mitosis, cell differentiation, and DNA damage repair [16]. Although it is a key player in injury repair and fetal development, the expression of PTTG1 is strictly regulated in normal cells. However, several studies have found that it is also highly expressed in many tumor tissues, such as pituitary tumors, breast cancer, thyroid cancer, digestive tract tumors, respiratory system tumors, and nervous system tumors [17,18]. It is worth noting that, although many studies have linked PTTG1 expression to tumors, the exact expression pattern and role of PTTG1 in OS remains elusive.

Our preliminary results showed that PTTG1 was highly expressed in OS cells. Therefore, it is essential to further investigate the expression and function of PTTG1 in OS. In this study, the correlation between the expression of PTTG1 in primary OS tissues and clinical manifestations was explored using clinical data. Furthermore, the mechanism of PTTG1-mediated regulation of downstream pathways was studied at multiple levels, such as in vitro functional experiments. Finally, in vivo tumorigenesis experiment was conducted to verify the above results and explore the molecular mechanism. We aimed to reveal the molecular mechanism of PTTG1 in mediating the biological behavior of OS malignancies and to provide new molecular targets and potential prognostic markers for the treatment of OS.