ARID3A knockdown facilitates ferroptosis partly through modulation of the PTEN/Akt pathway in breast cancer.

AT-rich interaction domain 3A (ARID3A) is a tumor regulator that modifies the PTEN and Akt pathway. The present study aimed to investigate the effect of ARID3A knockdown on ferroptosis and the interaction between ARID3A and the PTEN/Akt pathway in breast cancer. Firstly, MCF-7 and MDA-MB-231 cell lines were cultured. Negative control small interfering RNA (siNC) and ARID3A small interfering RNA (siARID3A) were transfected into the cells. Subsequently, siNC, PTEN small interfering RNA (siPTEN) and siARID3A were transfected into the cells alone or in combination. Comprehensive ferroptosis-associated indices were assessed. siARID3A transfection decreased cell viability, mitochondrial membrane potential (MMP) and glutathione peroxidase 4 (GPX4) expression, but increased the levels of malondialdehyde, reactive oxygen species (ROS) and ferrous iron (Fe2+), suggesting that siARID3A transfection promoted ferroptosis. Furthermore, siARID3A transfection upregulated PTEN expression and downregulated phosphorylated (p)-Akt levels, while siPTEN transfection elevated p-Akt levels and attenuated the effect of siARID3A transfection on p-Akt levels, indicating that siARID3A transfection modified the PTEN-mediated Akt pathway. In addition, siPTEN transfection increased cell viability, MMP and GPX4 expression, while decreasing ROS and Fe2+ levels. siPTEN transfection weakened the effect of siARID3A transfection on the majority of the aforementioned ferroptosis-associated indices, suggesting that PTEN was implicated in the function of ARID3A in ferroptosis. Overall, ARID3A knockdown promoted ferroptosis partly through modulation of the PTEN/Akt pathway in breast cancer. Despite this, further verification is still needed in future studies.