modulates proliferation and ferroptosis in mammary epithelial cells.

INTRODUCTION

, a transcriptionally active isoform of the gene, is essential for epithelial tissue development. Ferroptosis, a regulated form of cell death characterized by lipid peroxidation and reactive oxygen species (ROS) accumulation, has been increasingly studied in recent years. However, its role in epithelial cells and the regulatory function of in this context remain poorly understood.

METHODS

We investigated the role of in epithelial cell proliferation and ferroptosis using ectopic overexpression and RNA interference approaches. Cell proliferation was assessed through colony formation and DNA synthesis assays. Ferroptosis was induced using RSL3, and the effects were evaluated by measuring cell viability, ROS levels, and the expression of ferroptosis-associated genes and TFRC.

RESULTS

overexpression significantly increased expression, suppressed colony formation and DNA synthesis, thereby inhibiting cell proliferation. In contrast, knockdown reduced levels and enhanced cell proliferation. RSL3 treatment induced a dose-dependent increase in cell death and ROS accumulation, confirming the susceptibility of epithelial cells to ferroptosis. Furthermore, overexpression enhanced RSL3-induced ferroptosis by upregulating and , while knockdown diminished their expression, reducing oxidative stress and lipid peroxidation.

CONCLUSION

acts as a dual regulator of epithelial cell fate by inhibiting proliferation and promoting ferroptosis. These findings reveal a novel role for in epithelial cell biology and suggest potential therapeutic targets for diseases involving epithelial cell death.