Abstract
Purpose: To investigate the role of ATG7-induced autophagy in regulating ferroptosis and promoting the progression of colorectal adenocarcinoma (COAD). Method: The UALCAN database was used to predict the expression of ATG7 and its prognosis significance in patients with COAD. The expression levels of ATG7 in HCT8 and SW620 cells were analyzed using qPCR and Western blot analyses. Functional assays, including the CCK-8 and Transwell assays, were conducted to assess the effects of ATG7 overexpression on cell proliferation and migration. Protein-protein interaction analyses were performed using GeneMANIA and STRING to explore the relationships between ATG7, autophagy-related proteins, and markers of ferroptosis. Autophagy was inhibited using 3-MA, while ferroptosis was induced with erastin in ATG7-overexpressing COAD cells to elucidate their interactions. Results: Overexpression of ATG7 in COAD cells enhanced cell proliferation and migration, while inhibiting ferroptosis by decreasing levels of Fe2+ and MDA and increasing level of GSH. Mechanistically, ATG7-induced autophagy downregulated ACSL4 and upregulated GPX4, which are key regulators of ferroptosis. Pretreatment with 3-MA reversed these effects, thereby confirming the role of autophagy in modulating ferroptosis in COAD cells that overexpress ATG7. Conclusion: These findings suggest that targeting ATG7-mediated autophagy may serve as a therapeutic strategy for COAD by increasing susceptibility to ferroptosis-induced cell death.