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Updated: May 29, 2026
Revealing the Ferroptotic Phenotype of Medulloblastoma
Published on: March 15, 2024
MiR-144-3p enhances cisplatin sensitivity in triple-negative breast cancer by targeting SLC7A11 to induce ferroptosis
Rui Tian1, Mancheng Yu1, Hongtao Cheng1
1Department of Breast Surgery, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Provincial Clinical Research Center for Breast Cancer, Wuhan Clinical Research Center for Breast Cancer, Wuhan, Hubei, 430079, China.
Background:
Triple-negative breast cancer (TNBC) is an aggressive subtype in which resistance to cisplatin (cis-diamminedichloroplatinum II, CDDP) limits therapeutic efficacy, and ferroptosis has emerged as a key determinant of chemotherapy response. This study investigated the role of miR-144-3p in regulating CDDP sensitivity in TNBC and its underlying mechanism.
Methods:
MiR-144-3p expression was analyzed in TNBC tissues from CDDP-sensitive and -resistant patients. CDDP-resistant cell lines (MDA-MB-231/CDDP and BT-549/CDDP) were established by stepwise CDDP exposure and validated by increased IC50 values. Gain- and loss-of-function assays were performed using miR-144-3p mimic, si-SLC7A11, and SLC7A11 overexpression plasmids. Cell viability, clonogenic survival, and apoptosis were assessed by CCK-8, colony formation, and flow cytometry. Ferroptosis was evaluated by measuring lipid peroxidation (C11-BODIPY), ROS, GSH, Fe2+ levels, and GPX4 expression. Targeting of SLC7A11 by miR-144-3p was confirmed by dual-luciferase reporter assay and expression analysis. A xenograft model was used to assess tumor growth, SLC7A11 expression, and ferroptosis-related indicators in vivo.
Results:
MiR-144-3p was significantly downregulated in CDDP-resistant TNBC tissues and cells. Its restoration enhanced CDDP sensitivity and was associated with increased ferroptotic features, as evidenced by increased lipid peroxidation and ROS, decreased GSH, elevated Fe2+ levels, and reduced GPX4 expression. Mechanistically, miR-144-3p directly targeted SLC7A11. Rescue experiments showed that SLC7A11 overexpression attenuated ferroptosis and partially reversed CDDP sensitization. In vivo, miR-144-3p overexpression suppressed tumor growth, reduced SLC7A11 expression, and enhanced ferroptotic features.
Conclusion:
Our findings suggest that miR-144-3p enhances CDDP sensitivity in TNBC, at least in part, through regulation of the SLC7A11-mediated ferroptosis pathway, identifying a novel regulatory axis with therapeutic potential.
