The Essential Roles of Exosome and CircRNA_101093 to Desensitize Lung Adenocarcinoma to Ferroptosis

Abstract

BackgroundResistance to ferroptosis, a regulated cell death caused by iron-dependent excessive accumulation of lipid peroxides has recently been linked to lung adenocarcinoma (LUAD), the most prevalent lung cancer subtype. Despite intracellular antioxidant system is required for protection against ferroptosis, whether and how extracellular system desensitizes LUAD cells to ferroptosis is incompletely known. MethodsImmunohistochemistry (IHC) and immunoblotting (IB) were used to analyze protein expression, and quantitative RT-PCR (qPCR) was used to analyze mRNA level. Cell viability, cell death and the lipid reactive oxygen species (ROS) generation were measured to evaluate the responses to ferroptosis induction. Metabolites were measured using appropriate kits. Exosomes were observed using transmission electron microscope (TEM). The localization of arachidonic acid (AA) was detected using click chemistry labeling followed by confocal microscope observation. Interaction between RNA and protein were detected using RNA-pulldown, RNA immunoprecipitation (RIP) and photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP). Proteomic analysis was used to investigate circRNA_101093 (cir93) regulated protein and metabolomic analysis was used to analyze metabolites that changed among LUAD tissues expressing low and high Fatty acid-binding protein 3 (FABP3) levels. Cell-derived xenograft (CDX), patient-derived xenograft (PDX) and cell-implanted intrapulmonary LUAD mouse models and plasma/tissue specimens from LUAD patients were used to validate the mechanism that exosome and cir93 desensitized ferroptosis in LUAD. ResultsHere, the roles of exosome and circular RNA (circRNA) to desensitize LUAD cells to ferroptosis were investigated. Plasma exosome from LUAD patients exclusively reduced lipid peroxidation and desensitized ferroptosis. This might because exosomal-cir93 sustained an elevation of intracellular-cir93 in LUAD to modulate AA, a poly-unsaturated fatty acid that is critical for ferroptosis-associated over peroxidation in the plasma membrane. Mechanistically, cir93 interacted and lifted FABP3, which transported and facilitated AA reaction with taurine. Thus, global-AA was reduced while N-Arachidonoyl taurine (NAT), the product of AA and taurine, was induced. Notably, a role of NAT to suppress AA incorporation into plasma membrane was also revealed. In pre-clinical in vivo models, reducing exosome exhibited an improvement of ferroptosis-based treatment. ConclusionExosome and cir93 are essential for desensitizing LUAD cells to ferroptosis, and blocking exosome will be helpful for future LUAD treatment.

A survey on 3D object detection in real time for autonomous driving

“…An approach that uses a disentangling transformation for losses in detection, along with generating a confidence score based on self-supervised learning is proposed in (Simonelli et al, 2019) which do not need class labels. While (Zhang et al, 2023) introduces a framework that transforms into a depth-aware detection process and represents 3D object candidates through set queries. Then, an attention encoder based on depth is utilized to produce a non-local depth embedding from the image which was provided as input.…”

“…Several transformer-based frameworks, have already been presented in this survey, which include, MonoDTR (Huang et al, 2022), DST3D (Wu et al, 2022), and MonoDETr (Zhang et al, 2023). These frameworks have been used for precise depth inference or serves as feature backbones.…”