Mechanism of troxerutin-mediated regulation of EGLN3/LRPPRC in B[a]P-induced lung adenocarcinoma

Background Lung adenocarcinoma (LUAD) is the most prevalent and lethal subtype of lung cancer, exhibiting the highest incidence and mortality rates among all histological types. Although targeted therapy has shown promise, currently actionable genetic targets do not cover all LUAD cases, highlighting the need for novel therapeutic approaches. Method A malignant transformation model of lung epithelial cells (BEAS-2B-T) was established through repeated exposure to benzo[ a ]pyrene (B[ a ]P). Transcriptome sequencing was performed to identify key genes associated with carcinogenic transformation. Co-immunoprecipitation (Co-IP) coupled with high-performance liquid chromatography-mass spectrometry was utilized to determine proteins interacting with EGLN3. Potential therapeutic compounds targeting the EGLN3/LRPPRC axis were screened using the Topscience Database. The interaction between EGLN3, LRPPRC, and troxerutin was further investigated through multiple assays. Results EGLN3 was identified as a critical gene in B[ a ]P-induced LUAD, exhibiting significant overexpression in LUAD tissues and BEAS-2B-T cells, with an inverse correlation to patient survival. Silencing of EGLN3 markedly inhibited the proliferation, colony formation, migration, and invasion of LUAD and BEAS-2B-T cells. Overexpression of LRPPRC effectively reversed these inhibitory effects, indicating a functional interplay between EGLN3 and LRPPRC. Troxerutin was identified as a potential small-molecule compound targeting the EGLN3/LRPPRC axis and reducing their expression and interaction, thereby suppressing malignant behaviors of LUAD and BEAS-2B-T cells.