Super-enhancer-driven MLX mediates redox balance maintanance via SLC7A11 in osteosarcoma

A systematic analysis of super-enhancers identified MLX as a potential oncogene in osteosarcoma. Knockdown of MLX impaired tumor aggressiveness in vitro and in vivo, suggesting oncogenic properties of MLX. Mechanistically, silencing of MLX downregulates SLC7A11, a key gene encoding glutamate/cystine antiporter, to attenuate the uptake of cystine and interrupt the redox balance, leading to ferroptotic cell death. Pharmacological inhibition of SLC7A11 triggered massive ferroptosis and caused impaired tumor growth, providing a promising approach for osteosarcoma treatment. We performed shRNA-mediated knock-down of MLX in 143B cells. RNA isolation and unstranded RNA-seq library preparation were carried out using RNeasy Mini Kit (Qiagen) and NEBNext UltraTM RNA Library Prep Kit for Illumina, respectively.