The YY1-ABCB7 regulatory Axis is associated with malignant progression and ferroptosis sensitivity in lung adenocarcinoma.

AIM

Ferroptosis, a newly identified form of regulated cell death, has emerged as a promising therapeutic target in cancer treatment. The study was to clarify the regulatory effects of Yin Yang 1 (YY1) on ATP Binding Cassette Subfamily B Member 7 (ABCB7) expression and its related functions in lung adenocarcinoma (LUAD), focusing on ferroptosis.

METHODS

The bioinformatics analysis of ABCB7 expression in LUAD was initially conducted using public databases and subsequently validated through the examination of LUAD tissue samples. The effects of ABCB7 knockdown and YY1 overexpression on LUAD cell proliferation, migration, invasion, and sensitivity to ferroptosis were evaluated using a series of in vitro assays.

RESULTS

Elevated expression of ABCB7 in lung adenocarcinoma (LUAD) was significantly associated with poorer patient survival rates. Silencing of ABCB7 led to a marked reduction in LUAD cell proliferation, migration, and invasion, while concurrently inducing ferroptosis. Moreover, overexpression of YY1 was found to partially reverse these biological effects. Mechanistic investigations revealed that YY1 targets and activates the ABCB7 promoter, a conclusion supported by dual-luciferase assays. In vivo studies further confirmed that knockdown of ABCB7 inhibited LUAD cell proliferation and increased susceptibility to ferroptosis.

CONCLUSION

Our research suggests that YY1-mediated activation of ABCB7 may contribute to LUAD progression and potentially influences ferroptosis susceptibility. Targeting the YY1-ABCB7 axis emerges as a potential novel therapeutic approach for LUAD management.