CLTRN, Regulated by NRF1/RAN/DLD Protein Complex, Enhances Radiation Sensitivity of Hepatocellular Carcinoma Cells Through Ferroptosis Pathway

Purpose Radiation therapy is a viable treatment option for patients with unresectable hepatocellular carcinoma (HCC). However, radiation resistance and adverse effects are issues that needs to be addressed. Herein, the first time, we investigated ability of collectrin (CLTRN) enhance radiosensitivity in HCC. Methods Materials Transcriptome sequencing technology (RNA-seq technology) was used analyze transcription-level changes genes HepG2 cells before after x-ray irradiation. Combining results HCC tissue RNA-seq data, determined ultimate target gene through bioinformatics analysis cellular verification. A series molecular biology techniques were applied vitro vivo confirm whether CLTRN can cells. Subsequently, downstream action mechanism, upstream transcription factor, interaction proteins determined. Results First, confirmed verified association between radiosensitivity. In experiments performed. Investigation regulatory mechanism revealed analyzed at transcriptome level overexpression mostly enriched glutathione metabolic pathway. As metabolism forms vital link ferroptosis, surmised associated ferroptosis. This detection iron, determination reactive oxygen species levels, use transmission electron microscopy, monitoring ferroptosis-related protein indicators. Lastly, nuclear respiratory factor 1 dihydrolipoamide dehydrogenase members RAS oncogene family its interacting proteins. Conclusions regulator sensitivity could serve as novel therapeutic or prognostic marker treatment.