Inhibition of miR-301a-3p Expression Promotes Ferroptosis: A New Target for Ferroptosis Treatment in TNBC.

BACKGROUND: The current treatment of triple-negative breast cancer (TNBC) remains challenging; however, regulating ferroptosis through miRNAs offers new insights for TNBC treatment strategies. METHODS: Bioinformatics methods were used to screen ferroptosis-related differentially expressed genes (FRDEGs) in TNBC, and ferroptosis-related miRNAs were screened by combining gene-miRNA interaction network, miRNA survival analysis, and expression validation in clinical specimens. A nomogram was constructed to evaluate the prognostic impact of miR-301a-3p in TNBC. Cell proliferation and migration capabilities were assessed using the CCK-8 assay, colony formation assay, and wound healing assay, respectively. The intracellular protein expression of GPX4 was measured by Western blot, and fluorescent probes were used to detect intracellular ROS and Fe2+ levels. RESULTS: This study used bioinformatics methods to screen five FRDEGs in TNBC, thereby identifying six core miRNAs that can regulate these genes. Among these, miR-301a-3p expression was significantly upregulated in tumor tissues compared to adjacent normal tissues and was associated with poor patient prognosis. Subsequently, an excellent prediction model was established using miR-301a-3p expression information and patient clinicopathological information. Functional analyses revealed that miR-301a-3p promoted TNBC cell proliferation and migration. In addition, the inhibition of cell proliferation activity by miR-301a-3p inhibitor could be reversed by Ferrostatin-1, and miR-301a-3p inhibitor could inhibit the expression of GPX4 and promote the accumulation of intracellular ROS and Fe2+. The promotion of cell proliferation activity by miR-301a-3p mimic could be reversed by Erastin, and miR-301a-3p mimic could promote the expression of GPX4 and inhibit the accumulation of intracellular ROS and Fe2+. CONCLUSION: In conclusion, this study provides evidence that inhibition of miR-301a-3p expression promotes ferroptosis in TNBC cells and produces a synergistic anti-cancer effect with Erastin, providing a new target for future TNBC ferroptosis treatment strategies.