ZFP36 suppresses lung adenocarcinoma progression by mediating ROS-induced autophagy and ferroptosis

As a tumor suppressor in lung adenocarcinoma (LUAD), ZFP36 is an RNA-binding protein that destabilizes oncogenic mRNAs. However, the precise mechanisms underlying its tumor-suppressive function remain mostly unexplored. The study aims to explore the molecular mechanisms by which ZFP36 suppresses LUAD progression through regulating reactive oxygen species (ROS)-mediated ferroptosis and autophagy.

Real-time quantitative PCR and Western blotting were utilized to investigate ZFP36 expression in cell lines, adjacent normal tissues, and LUAD tissues. Using MTT, colony formation, and apoptosis assays, the impact of ZFP36 overexpression or knockdown on cell proliferation and apoptosis was evaluated. ROS levels and ferroptosis-related markers (MDA, 4-HNE, total iron, and Fe²⁺) were measured in A549 cells. Proteins associated with ferroptosis and autophagy were evaluated for expression using Western blotting.

ZFP36 expression was markedly reduced in LUAD cell lines and tissues (P < 0.05). ZFP36 overexpression triggered autophagy and ferroptosis, apoptosis, and inhibited cell proliferation in A549 cells (P < 0.05). Mechanistically, ZFP36 upregulated ROS levels, which in turn induced autophagy and ferroptosis-associated changes, as indicated by increased Beclin-1, ATG5, and the LC3B-II/LC3B-I ratio, ACSL4, and lipid peroxidation markers, along with decreased GPX4 and SLC7A11 expression (P < 0.05).

ZFP36 suppresses LUAD progression by promoting ROS-mediated autophagy and ferroptosis-associated changes. As per the results, ZFP36 may be a useful biomarker and treatment target for the treatment of LUAD.