Inhibition of BUB1 suppresses tumorigenesis of osteosarcoma via blocking of PI3K/Akt and ERK pathways

Abstract

Osteosarcoma (OS) is a primary malignant bone tumour that mainly affects teenagers, with patients displaying poor prognosis. Budding uninhibited by benzimidazoles 1 (BUB1), a type of serine/threonine kinase that is linked to pro‐tumorigenic phenomena, has not been well studied in OS. Hence, this study aimed to explore the role of BUB1 in OS. The expression of BUB1 in OS specimens and cell lines was assessed using immunohistochemistry and Western blot analysis. Univariate and multivariate analyses were applied to evaluate the impact of BUB1 on patient survival. Cell counting kit‐8, wound‐healing and Transwell assays, as well as flow cytometry, were used to investigate the influence of BUB1 inhibition on OS in vitro. Moreover, a tumour xenograft model was established to investigate the in vivo effect of BUB1 inhibition on OS tumour growth. Results showed that BUB1 was overexpressed in OS specimens and cell lines. Furthermore, BUB1 overexpression was closely associated with the poor clinical outcomes of patients with OS. Inhibition of BUB1 markedly suppressed cell proliferation and tumour growth, cell migration, invasion and induced cell apoptosis of OS by blocking the PI3K/Akt and ERK signalling pathways. Thus, our study suggested that overexpression of BUB1 protein contributed to poor survival of OS patients and that inhibition of BUB1 resulted in considerable anti‐tumour activity associated with proliferation, migration, invasion and apoptosis of OS.

circ-RANGAP1/MicroRNA-542-3p/Myosin Regulatory Light Chain Interacting Protein Axis Modulates the Osteosarcoma Cell Progression

“…OS is manifested with elevated metastasis rate and poor prognosis and is hardly treated because of limited treatment strategies [ 1 , 2 ]. Consequently, it is vital to further realize the molecular mechanism of OS occurrence and development.…”

“…Osteosarcoma (OS) is the most prevalent primary invasive bone tumor, frequently existing in young men and children under 20 years of age. Like other tumors, OS has a high degree of malignancy, many OS patients are prone to recurrence or metastasis, and the prognosis is poor [ 1 ]. Although surgical techniques and chemotherapy have improved in recent years, the survival rate of many patients has not improved much, and the 5-year survival rate is still less than 70% [ 2 ].…”

Environmentally Relevant Concentrations of Tris(1,3-dichloro-2-propyl) Phosphate Induced a Female-Biased Osteotoxicity in Crucian Carp (Carassius auratus)

“…Based on PPI network, genes with top 5 highest degree were identified, including cdk1 , cdc20 , bub1 , plk1 , and aurkb. In human clinical studies, cdk1 , cdc20 , bub1 , and plk1 were commonly associated with bone diseases, including rheumatoid arthritis, osteoarthritis, and bone-related tumors. − Therefore, these results indicated that aberrant expression of the selected hub genes might be responsible for caudal malformation in this study. Our results highlighted the negative effects of TDCIPP on the skeletal system of fish.…”

Identification and Validation of a Potential Stemness-Associated Biomarker in Hepatocellular Carcinoma

“…In addition, transforming growth factor- β (TGF- β ) signal transduction, which regulates cell proliferation and differentiation, may be regulated by BUB1 [ 44 ]. In osteosarcoma, inhibition of BUB1 markedly suppressed cell proliferation, cell migration, and invasion through blocking of the PI3K/Akt and ERK signaling pathways [ 45 ]. Our results confirmed that BUB1 plays a vital role in the regulation of MYC, Wnt, Notch, and Hedgehog pathways, which are sharply associated with stemness signaling [ 6 , 8 ].…”