Clinical and Translational Medicine, Год журнала: 2024, Номер 14(10)

Опубликована: Окт. 1, 2024

Abstract Background Radiotherapy is a primary therapeutic modality for esophageal squamous cell carcinoma (ESCC), but its effectiveness still restricted due to the resistance of cancer cells radiation. Long non‐coding RNAs (lncRNAs) and N 6 ‐methyladenosine (m6A) have been shown play significant roles in tumour radioresistance. However, precise manifestation role m6A‐modified lncRNAs ESCC radioresistance remain unclear. Methods Bioinformatics analysis was conducted identify implicated ESCC. A series functional experiments were performed investigate function LNCAROD Methylated RNA immunoprecipitation, chromatin isolation by purification‐mass spectrometry, co‐immunoprecipitation explore mechanism m6A‐mediated upregulation expression downstream enhancing The efficacy vivo assessed using murine xenograft models. Results Herein, we identified as novel METTL3‐mediated lncRNA that enhanced post‐transcriptionally stabilised YTHDC1. Moreover, confirmed prevented ubiquitin‐proteasome degradation PARP1 protein facilitating PARP1‐NPM1 interaction, thereby contributing homologous recombination‐mediated DNA double‐strand breaks repair radiation cells. Silencing nude mouse model resulted slower growth increased radiosensitivity. Conclusion Our findings enhance understanding lncRNA‐driven machinery underscore significance this context, development potential target patients.

Язык: Английский