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- Title
Linc-RA1 inhibits autophagy and promotes radioresistance by preventing H2Bub1/USP44 combination in glioma cells.
- Authors
Zheng, Jieling; Wang, Baiyao; Zheng, Rong; Zhang, Jian; Huang, Chunyue; Zheng, Ronghui; Huang, Zhong; Qiu, Wenze; Liu, Mengzhong; Yang, Kaijun; Mao, Zixu; Ji, Aimin; Yuan, Yawei
- Abstract
Radiotherapy is one of the standard treatments for glioma patients; however, its clinical efficacy is limited by radioresistance. We identified a mechanism of such resistance mediated by linc-RA1 (radioresistance-associated long intergenic noncoding RNA 1). Linc-RA1 was upregulated in radioresistant glioma cells and glioma tissue samples, compared with radiosensitive cells and nontumor tissues. Linc-RA1 was associated with inferior overall survival and advanced clinical stage of glioma. Linc-RA1 promoted glioma radioresistance in vitro and in vivo. Mechanistically, linc-RA1 stabilized the level of H2B K120 monoubiquitination (H2Bub1) by combining with H2B and inhibiting the interaction between H2Bub1 and ubiquitin-specific protease 44 (USP44), which inhibited autophagy, thus contributing to glioma radioresistance. These results reveal that linc-RA1-mediated autophagy is a key mechanism of radioresistance and is an actionable target for improving radiotherapy efficacy in patients with glioma.
- Publication
Cell Death & Disease, 2020, Vol 11, Issue 9, p1
- ISSN
2041-4889
- Publication type
Article
- DOI
10.1038/s41419-020-02977-x