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- Title
The super-enhancer-driven lncRNA LINC00880 acts as a scaffold between CDK1 and PRDX1 to sustain the malignance of lung adenocarcinoma.
- Authors
Feng, Yipeng; Zhang, Te; Zhang, Zeyu; Liang, Yingkuang; Wang, Hui; Chen, Yuzhong; Yu, Xinnian; Song, Xuming; Mao, Qixing; Xia, Wenjie; Chen, Bing; Xu, Lin; Dong, Gaochao; Jiang, Feng
- Abstract
Super-enhancers (SEs) are regulatory element clusters related to cell identity and disease. While the studies illustrating the function of SE-associated long noncoding RNAs (lncRNAs) in lung adenocarcinoma (LUAD) remains few. In our research, a SE-driven lncRNA, LINC00880, was identified, which showed higher expression in LUAD compared to normal tissues and indicated worse outcomes in stage I LUADs. We found that the transcription factor (TF) FOXP3 could simultaneously occupy the promoter and SE regions of LINC00880 to promote its transcription. The oncogenic function of LINC00880 was validated both in vitro and in vivo. Mechanically, LINC00880 binds to the protein CDK1 to increase its kinase activity, which rely on the phosphorylation state of pT161 in CDK1. LINC00880 also promotes the interaction between CDK1 and PRDX1. Moreover, LINC00880 interacts with PRDX1, which indicates that LINC00880 acts as a protein scaffold between CDK1 and PRDX1 to form a ternary complex, thereby resulting in the activation of PI3K/AKT to promote malignancy. Our results reveal that the SE-associated lncRNA LINC00880 regulates the CDK1/PRDX1 axis to sustain the malignancy of LUAD, providing a novel therapeutic target. Highlights: LINC00880 is driven by Super-enhancer. LINC00880 interacts with CDK1 to activate its kinase activity. LINC00880 acts as the protein scaffold between CDK1 and PRDX1.
- Publication
Cell Death & Disease, 2023, Vol 14, Issue 8, p1
- ISSN
2041-4889
- Publication type
Article
- DOI
10.1038/s41419-023-06047-w