ADAR1 Promotes the Progression and Temozolomide Resistance of Glioma Through p62‐Mediated Selective Autophagy

作者：Yuyan Zhang, Huiling Guo, Jiahao Bu, Weiwei Wang, Li Wang, Zhibo Liu, Yuning Qiu, Qimeng Wang, Lijuan Zhou, Xianzhi Liu, Liwei Ma, Jianwei Wei · 发表于：CNS Neuroscience & Therapeutics · 年份：2025 · DOI：10.1111/cns.70168 · 被引用次数：5 · 研究领域：RNA regulation and disease、Endoplasmic Reticulum Stress and Disease、Amyotrophic Lateral Sclerosis Research

BACKGROUND: Resistance to temozolomide (TMZ) remains is an important cause of treatment failure in patients with glioblastoma multiforme (GBM). ADAR1, as a member of the ADAR family, plays an important role in cancer progression and chemotherapy resistance. However, the mechanism by which ADAR1 regulates GBM progression and TMZ resistance is still unclear. METHODS: We first constructed stable transfected strains in which ADAR1 was knocked down and overexpressed to investigate the effect of ADAR1 on the first-line glioma chemotherapy drug TMZ. Subsequently, we validated that ADAR1 induces autophagy activation and used autophagy inhibitors to suppress autophagy, demonstrating that ADAR1 enhances TMZ resistance through autophagy. We further knocked down p62 (SQSTM1) based on the overexpression of ADAR1, and the results showed that ADAR1 regulates selective autophagy through the p62 regulation. Finally, we demonstrated through mutations at both edited and nonedited sites that ADAR1 regulates selective autophagy in an edited dependent way. RESULTS: Further analysis showed that in the presence of TMZ, elevated ADAR1 promoted TMZ induced autophagy activation. Further research revealed that ADAR1 enhances TMZ resistance through p62-mediated selective autophagy. Further, ADAR1 regulates selective autophagy in an edited dependent way. Our results indicate a relationship between ADAR1 levels and the response of glioma patients to TMZ treatment. CONCLUSIONS: We found that the expression ...