Super-enhancer-driven lncRNA LIMD1-AS1 activated by CDK7 promotes glioma progression

• Published in: Cell death & disease Vol. 14; no. 6; p. 383
• Main Authors: Chen, Zhigang, Tian, Dasheng, Chen, Xueran, Cheng, Meng, Xie, Han, Zhao, JiaJia, Liu, Jun, Fang, Zhiyou, Zhao, Bing, Bian, Erbao
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29-06-2023; Springer Nature B.V; Nature Publishing Group
• Subjects: 13/109; 13/44; 13/89; 14/32; 631/337; 64/60; 692/699/67; Antibodies; Apoptosis; Biochemistry; Biomedical and Life Sciences; Brain; Brain research; Cell Biology; Cell Culture; Cell migration; Cell proliferation; Colonies; Cyclin-Dependent Kinases; Datasets; DNA methylation; Gene expression; Glioma; Glioma - genetics; Glioma cells; GRP78 protein; Hospitals; Humans; Immunology; Intracellular Signaling Peptides and Proteins - genetics; Laboratories; Life Sciences; LIM Domain Proteins - genetics; Liver cancer; Medical prognosis; Non-coding RNA; Patients; Proteins; Regulatory Sequences, Nucleic Acid; RNA, Long Noncoding - genetics; Transcription factors
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-023-05892-z

Long non-coding RNAs (lncRNAs) are tissue-specific expression patterns and dysregulated in cancer. How they are regulated still needs to be determined. We aimed to investigate the functions of glioma-specific lncRNA LIMD1-AS1 activated by super-enhancer (SE) and identify the potential mechanisms. In this paper, we identified a SE-driven lncRNA, LIMD1-AS1, which is expressed at significantly higher levels in glioma than in normal brain tissue. High LIMD1-AS1 levels were significantly associated with a shorter survival time of glioma patients. LIMD1-AS1 overexpression significantly enhanced glioma cells proliferation, colony formation, migration, and invasion, whereas LIMD1-AS1 knockdown inhibited their proliferation, colony formation, migration, and invasion, and the xenograft tumor growth of glioma cells in vivo. Mechanically, inhibition of CDK7 significantly attenuates MED1 recruitment to the super-enhancer of LIMD1-AS1 and then decreases the expression of LIMD1-AS1. Most importantly, LIMD1-AS1 could directly bind to HSPA5, leading to the activation of interferon signaling. Our findings support the idea that CDK7 mediated-epigenetically activation of LIMD1-AS1 plays a crucial role in glioma progression and provides a promising therapeutic approach for patients with glioma.