Bivalent activity of super-enhancer RNA LINC02454 controls 3D chromatin structure and regulates glioma sensitivity to temozolomide

• Published in: Cell death & disease Vol. 15; no. 1; p. 6
• Main Authors: Shi, Tengfei, Guo, Dianhao, Zheng, Yaoqiang, Wang, Wenbin, Bi, Jinfang, He, Anshun, Fan, Sibo, Su, Guangsong, Zhao, Xueyuan, Zhao, Zhenhao, Song, Yingjie, Sun, Shupeng, Li, Peng, Zhao, Zhongfang, Shi, Jiandang, Lu, Wange, Zhang, Lei
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.01.2024; Springer Nature B.V; Nature Publishing Group
• Subjects: 38; 38/23; 38/91; 45/15; 45/77; 45/90; 631/67/69; 631/80/82; Antibodies; Biochemistry; Biomedical and Life Sciences; Brain cancer; Cell Biology; Cell Culture; Cells; Chromatin; Cloning; Cytotoxicity; Data analysis; Gene expression; Genomes; Glioma; Glioma cells; Immunology; Life Sciences; Plasmids; Reagents; Ribonucleic acid; RNA; Temozolomide
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-023-06392-w

Glioma cell sensitivity to temozolomide (TMZ) is critical for effective treatment and correlates with patient survival, although mechanisms underlying this activity are unclear. Here, we reveal a new mechanism used by glioma cells to modulate TMZ sensitivity via regulation of SORBS2 and DDR1 genes by super-enhancer RNA LINC02454 . We report that LINC02454 activity increases glioma cell TMZ sensitivity by maintaining long-range chromatin interactions between SORBS2 and the LINC02454 enhancer. By contrast, LINC02454 activity also decreased glioma cell TMZ sensitivity by promoting DDR1 expression. Our study suggests a bivalent function for super-enhancer RNA LINC02454 in regulating glioma cell sensitivity to TMZ.