Male-specific lethal 1 (MSL1) promotes Erastin-induced ferroptosis in colon cancer cells by regulating the KCTD12-SLC7A11 axis

Abstract MSL1, a scaffold protein of the histone acetyltransferase MSL complex, plays a crucial role in the structural integrity and enzyme activity of the complex. Although it has shown that MSL1 is highly expressed in various primary tumor tissues, its role and molecular mechanism in the occurrence and development of tumors, as well as its impact on the process of tumor cell death, are not yet fully understood. Herein, we presence evidence for the first time from systematic biochemical assays and knockdown/overexpression approaches arguing that a negative regulatory mechanism exists between MSL1 and KCTD12. Interestingly, in HCT116 colon cancer cells, the expression of MSL1 was dramatically inhibited by the ferroptosis inducer Erastin, leading to upregulation of KCTD12 expression. Meanwhile, MSL1 promotes Erastin induced ferroptosis in HCT116 cells by regulating the KCTD12-SLC7A11 axis. In line with this, the ROS, GSH, and MDA levels induced by Erastin were impacted by the MSL1-KCTD12-SLC7A axis, suggesting the involvement of this axis in Erastin induced ferroptosis in colon cancer cells. Our findings will provide new therapeutic targets and theoretical basis for clinical colon cancer.