Endometriosis is a chronic disorder characterized by the implantation of endometrial glands and stroma outside the uterus. However, the pathogenesis of
endometriosis is still unclear. To date, there is no fully effective treatment without
trauma because of various side effects. Recent data suggest that ferroptosis is a novel recognized form of nonapoptosis-regulated cell death characterized by
iron-dependent and lethal lipid peroxidation accumulation, showing great promise in the treatment of many diseases. In the present study, we verified that
erastin induced ferroptosis in ectopic endometrial stromal cells (EESCs). Furthermore, we found that the expression of
metastasis-associated
lung adenocarcinoma transcript 1 (MALAT1) was decreased during
erastin-induced ferroptosis. Knockdown of MALAT1 significantly aggravated the inhibition of cell viability and increased intracellular
iron, Liperfluo, and MDA levels in EESCs upon
erastin treatment. Mechanistically, we demonstrated that MALAT1 served as a
competing endogenous RNA of miR-145-5p to regulate the expression of MUC1, a suppressor of ferroptosis. MALAT1 knockdown-mediated ferroptotic cell death and MUC1 downregulation could be abrogated by inhibition of miR-145-5p. In addition, miR-145-5p inhibition-mediated ferroptotic cell death could be abolished by MUC1 knockdown. Furthermore,
erastin-induced ferroptosis shrunk endometriotic lesions via the MALAT1/miR-145-5p/MUC1 axis in vivo. Taken together, our data indicate that knockdown of MALAT1 facilitates ferroptosis upon
erastin treatment via miR-145-5p/MUC1 signaling. The synergistic effect of MALAT1 knockdown and
erastin induction in ferroptosis may be a new therapeutic strategy for
endometriosis.