Downregulation of MGAT3 Promotes Benzo[a]pyrene-Mediated Lung Carcinogenesis by Regulating Cell Invasion and Migration Activity.

Environmental chemical carcinogens are major factors in the induction of lung cancer, with benzo[a]pyrene (B[a]P) being one of the most widespread and highly carcinogenic among them. Although studies have reported that B[a]P exerts its carcinogenic effects by causing mutations, inducing cytotoxicity, and inhibiting DNA synthesis, the early molecular regulatory events and mechanisms involved in B[a]P-induced tumor initiation remain unclear. This study found that the MGAT3 gene was significantly downregulated in B[a]P-induced mouse lung tumorigenesis, suggesting its important tumor-suppressive function. Further investigation revealed that suppression of MGAT3 expression promoted the invasion and migration abilities of lung cancer cells, while overexpression of MGAT3 in these cells inhibited these effects. Western blot analysis also showed that MGAT3 regulated the expression of epithelial-mesenchymal transition markers, thereby affecting the motility of lung cancer cells. Xenograft assay also confirmed the inhibitory effect of MGAT3 overexpression on tumor proliferation. Analysis of lung cancer tissue expression further validated that MGAT3 is significantly downregulated in lung cancer tissues, and this decrease in expression is associated with a poor prognosis in lung cancer patients. Our research indicates that the suppression of MGAT3 expression and its downstream regulatory molecules plays a crucial role in lung cancer development induced by environmental chemical carcinogens.