ELOVL5 Regulates Ferroptosis in Breast Cancer Cells

Today, breast cancer (BC) occupies a leading position in prevalence and mortality from oncological diseases among the female population worldwide. Ferroptosis is a special type of cell death associated with peroxidation of intracellular lipids. It is a promising option for the therapy of BC resistant to traditional methods of treatment. The ELOVL5 gene, involved in the elongation of long-chain polyunsaturated fatty acids (LC-PUFA), was previously associated with BC progression. In this work, the effect of ELOVL5 knockdown on the dynamics of ferroptosis induction in MDA-MB-231 cells under the influence of docosahexaenoic acid (DHA) and erastin was investigated. A comparative analysis of changes in the expression of individual genes under the influence of these agents was also carried out. It was shown that a decrease in ELOVL5 expression increases cell sensitivity to both agents, while DHA causes earlier cell death. The protective effect of ferroptosis inhibitors (ferrostatin-1 and deferoxamine) confirmed the involvement of this pathway in the observed effects. Differences in the expression of genes associated with oxidative stress, inflammation and proliferation were also revealed, indicating different molecular trajectories of ferroptosis in cells with different ELOVL5 gene expression. Thus, the present study deepens the understanding of the contribution of the ELOVL5 gene to the regulation of ferroptosis and can be used in the development of targeted therapy for breast cancer.