B-cell specific Moloney murine leukemia virus insertion site 1 contributes to invasion, metastasis, and poor prognosis in salivary adenoid cystic carcinoma

J Dent Sci. 2024 Jan;19(1):21-31. doi: 10.1016/j.jds.2023.06.014. Epub 2023 Jun 24.

Abstract

Background/purpose: Upregulation of B-cell specific Moloney murine leukemia virus insertion site 1 (BMI-1) has been involved in the invasion, metastasis, and poor prognosis of many cancers. The aim of this study was to evaluate the levels and clinical significance of BMI-1 in saliva of patients with salivary adenoid cystic carcinoma (SACC), and to analyze biological function and mechanism of BMI-1 in the invasion and metastasis of SACC.

Materials and methods: The levels of BMI-1 in saliva and tumor tissues of SACC patients were determined. The correlation of salivary BMI-1 levels with clinicopathological parameters and clinical outcomes in patients with SACC was analyzed. Additionally, the effects of BMI-1 on wound-healing, transwell invasion, and epithelial-mesenchymal transition (EMT)-related protein expression in vitro as well as on tumorigenicity and experimental lung metastasis in vivo were investigated through exogenous overexpression and silencing of BMI-1 in SACC cells.

Results: BMI-1 levels increased in saliva and tumor tissues in SACC patients with invasion or metastasis. High salivary BMI-1 levels were correlated with poor TNM stage, poor overall survival, and disease-free survival. Exogenous expression of BMI-1 in SACC-83 promoted its migration and invasion, while silencing BMI-1 in SACC-LM inhibited its migration and invasion in vitro and suppressed tumorigenesis and lung metastasis in vivo. Furthermore, BMI-1 regulated the expression of EMT-related proteins in SACC.

Conclusion: Our study shows that BMI-1 can serve as a valuable biomarker to identify tumor invasion and metastasis in SACC, predict its prognosis, and act as a promising therapeutic target for SACC.

Keywords: Adenoid cystic carcinoma; BMI-1; Invasion; Metastasis; Prognostic predictor; Salivary gland.