BAI1 acts as a tumor suppressor in lung cancer A549 cells by inducing metabolic reprogramming via the SCD1/HMGCR...

Area of Science:

• Oncology
• Cancer Metabolism
• Molecular Biology

Background:

• Brain-specific angiogenesis inhibitor 1 (BAI1) is a known tumor suppressor, but its role in lung cancer and metabolic regulation is unclear.
• Tumorigenesis involves metabolic reprogramming, including the Warburg effect and altered glycolysis, which are critical for cancer cell survival and proliferation.

Purpose of the Study:

• To investigate the anti-tumor effects of BAI1 in lung cancer A549 cells.
• To elucidate the relationship between BAI1 and metabolic reprogramming in lung cancer.
• To identify key molecules regulated by BAI1 involved in metabolic alterations.

Main Methods:

• Immunohistochemistry to correlate BAI1 expression with lung cancer prognosis.
• Generation of BAI1-overexpressing (BAI1-OE) and control A549 cell lines via lentiviral transfection.
• In vitro functional assays (proliferation, apoptosis, colony formation, invasion) and in vivo metastasis assays.
• Seahorse assay to measure glycolytic rate and Warburg effect.
• Analysis of stearoyl-CoA desaturase 1 (SCD1) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) expression.

Main Results:

• Lower BAI1 expression in tumor tissues is associated with poor lung cancer prognosis.
• Overexpression of BAI1 significantly inhibited proliferation, migration, invasion, colony formation, and in vivo metastasis of A549 cells.
• BAI1 overexpression suppressed the Warburg effect and glycolysis, indicating metabolic reprogramming.
• BAI1 upregulated SCD1 and downregulated HMGCR, mediating metabolic reprogramming.

Conclusions:

• BAI1 functions as a tumor suppressor in lung cancer by inhibiting proliferation and metastasis.
• BAI1 induces metabolic reprogramming in lung cancer cells by suppressing the Warburg effect and glycolysis.
• The novel mechanism involves BAI1 regulating SCD1 and HMGCR, highlighting a new therapeutic target.