# PAX6 Downregulation Triggers HIF-1α-Mediated Ferroptosis in Glioma Cells

## TL;DR

This study shows that lower levels of PAX6 in glioma cells lead to increased ferroptosis, a form of cell death, through the HIF-1α pathway.

## Contribution

The novel finding is that PAX6 downregulation promotes ferroptosis in glioma cells by modulating HIF-1α and antioxidant systems.

## Key findings

- PAX6 inhibits HIF-1α expression by regulating reactive oxygen species levels.
- Overexpression of PAX6 increases lipid peroxides and decreases GPX4 and GSH in glioma cells.
- Downregulation of PAX6 is linked to ferroptosis regulation in glioma.

## Abstract

Background: The paired-box gene 6 (PAX6) is an important transcription factor in the central nervous system, mainly regulating the development and differentiation of embryonic eyes and the nervous system. PAX6 expression is significantly decreased in glioma, and the expression levels are closely related to glioma development and prognosis. Therefore, it is important to study and elucidate the biological function of PAX6 in glioma to further our understanding of the occurrence and development of glioma. Methods: This study focused on the expression and regulation of PAX6 and hypoxia-inducing factor (HIF-1α) and investigated the molecular mechanism of ferroptosis regulated by PAX6 and HIF-1α. Firstly, immunohistochemistry, qPCR, Western blot, and other methods were used to detect PAX6 and HIF-1α expression in glioma tissues and cells, as well as the specific way in which PAX6 regulates HIF-1α. Then, some relative indicators of ferroptosis regulated by PAX6 in glioma were studied. Results: The results showed that PAX6 inhibited HIF-1α expression by regulating the levels of reactive oxygen species (ROS); overexpression of PAX6 promoted the expression of ROS and lipid peroxides (LPOs) in glioma cells and decreased the expression of intracellular antioxidant systems glutathione peroxidase 4 (GPX4) and glutathione (GSH). Conclusions: Downregulation of PAX6 plays an important role in regulating ferroptosis in glioma cells. Our research provides a reference basis for a deeper understanding of the role of PAX6 in ferroptosis of glioma.