LINC01770 stabilizes TEAD1 expression to mediates nasopharyngeal cancer radiation resistance rendering tumor cells vulnerable to ferroptosis

Abstract Background Long noncoding RNAs (lncRNAs) regulate various essential biological processes, including cell proliferation, differentiation, apoptosis, migration, and invasion. However, in nasopharyngeal carcinoma (NPC), the clinical significance and mechanisms of lncRNAs in malignant progression are unknown. Methods LINC01770 expression was determined using quantitative real-time reverse transcription PCR, and its prognostic value was evaluated using Kaplan-Meier survival analysis. RNA sequencing and bioinformatic analysis were used to determine the potential function of LINC01770, and its biological effects were investigated using in vitro and in vivo experiments. Mass spectrometry-coupled RNA pull-down assays and western blotting identified LINC01770 interacting proteins, followed by confirmation using RNA immunoprecipitation (RIP) assays. Ferroptosis and lipid peroxidation were detected using flow cytometry. Results LINC01770 was overexpressed in NPC tissues according to microarray screening. Patients with NPC showing high LINC01770 expression experienced shorter survival and worse prognosis. In vitro and in vivo experiments suggested that knockdown of LINC01770 expression significantly inhibited the proliferation, migration, and invasion of NPC cells. Sequencing and functional complementation experiments showed that LINC01770 regulates the proliferation and metastasis of NPC through TEA domain transcription factor 1 (TEAD1). Meanwhile, RIP and PCR experiments suggested that LINC01770 and TEAD1 were common targets of microRNAs miR-615-5p and miR-1293. Overexpression of LINC01770 promoted ferroptosis in vitro and in vivo through the TEAD1/Acyl-CoA synthetase long chain family member 4 (ACSL4)/transferrin receptor (TFRC) pathway. Conclusions LINC01770 is a prognostic biomarker for NPC and participates in the regulation of TEAD1 signaling pathway through competitive binding to miRNA-615-5p and miRNA-1293, resulting in NPC metastasis and progression. Radiation resistant cells are in a delicate balance between lipid peroxidation and increased vulnerability to ferroptosis, suggesting that ferroptosis could be used to kill NPC cells and reverse their radiotherapy resistance during the malignant progression of NPC caused by high expression of LINC01770. Thus, inducing ferroptosis could be used to treat recurrent and refractory NPC.