Essential roles of exosome and circRNA_101093 on ferroptosis desensitization in lung adenocarcinoma

作者：Xiao Zhang, Yunhua Xu, Lifang Ma, Keke Yu, Yongjie Niu, Xin Xu, Yi Shi, Susu Guo, Xiangfei Xue, Yikun Wang, Shiyu Qiu, Jiangtao Cui, Hong Wang, Xiaoting Tian, Yayou Miao, Fanyu Meng, Yongxia Qiao, Yongchun Yu, Jiayi Wang · 发表于：癌症：英文版 · 年份：2022 · DOI：10.1002/cac2.12275 · 被引用次数：196 · 研究领域：Ferroptosis and cancer prognosis、Cancer-related molecular mechanisms research、Circular RNAs in diseases

BACKGROUND: Resistance to ferroptosis, a regulated cell death caused by iron-dependent excessive accumulation of lipid peroxides, has recently been linked to lung adenocarcinoma (LUAD). Intracellular antioxidant systems are required for protection against ferroptosis. The purpose of the present study was to investigate whether and how extracellular system desensitizes LUAD cells to ferroptosis. METHODS: Established human lung fibroblasts MRC-5, WI38, and human LUAD H1650, PC9, H1975, H358, A549, and H1299 cell lines, tumor and matched normal adjacent tissues of LUAD, and plasma from healthy individuals and LUAD patients were used in this study. Immunohistochemistry and immunoblotting were used to analyze protein expression, and quantitative reverse transcription-PCR was used to analyze mRNA expression. Cell viability, cell death, and the lipid reactive oxygen species generation were measured to evaluate the responses to ferroptosis. Exosomes were observed using transmission electron microscope. The localization of arachidonic acid (AA) was detected using click chemistry labeling followed by confocal microscopy. Interactions between RNAs and proteins were detected using RNA pull-down, RNA immunoprecipitation and photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation methods. Proteomic analysis was used to investigate RNA-regulated proteins, and metabolomic analysis was performed to analyze metabolites. Cell-derived xenograft, patient-derived xenograft, c...