Key Early Changes in Oral Squamous Cell Carcinogenesis Are Accelerated by Ectopic BMI1 Expression

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Oral squamous cell carcinoma (OSCC) diagnosis often occurs at late stages, despite moderate survival rate increases.
• B cell-specific Moloney murine leukemia virus integration site 1 (BMI1) is an OSCC biomarker elevated in premalignant lesions' stem cells.
• The precise role of BMI1 in early-stage OSCC remains incompletely understood.

Purpose of the Study:

• To investigate the molecular functions of BMI1 in the early stages of oral squamous cell carcinoma (OSCC).
• To delineate the role of BMI1 in carcinogen-induced oral tumorigenesis using a transgenic mouse model.

Main Methods:

• Utilized a KrTB transgenic mouse line overexpressing BMI1 in tongue epithelial stem cells.
• Administered 4-nitroquinoline 1-oxide (4-NQO) carcinogen for 4 weeks to assess BMI1's role in early oncogenesis.
• Employed a human OSCC cell line (SCC-25) to study the effects of BMI1 gene deletion.

Main Results:

• Ectopic BMI1 expression accelerated oncogenic changes, including increased proliferation and oxidative stress, after short-term carcinogen exposure.
• BMI1 overexpression potentiated the upregulation of metabolic targets like SLC16A3, PKM, and GPI1 in response to 4-NQO.
• BMI1 gene deletion in human OSCC cells reduced proliferation, oxidative stress, and GLUT1 expression.

Conclusions:

• BMI1 promotes key features of early-stage, carcinogen-induced oral tumorigenesis, notably metabolic reprogramming.
• Limiting BMI1 activity presents a potential therapeutic target for oral cancer prevention strategies.
• Further functional studies are warranted to explore BMI1's role in cancer development.