Cell Death and Disease (Jan 2024)

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

  • Tengfei Shi,
  • Dianhao Guo,
  • Yaoqiang Zheng,
  • Wenbin Wang,
  • Jinfang Bi,
  • Anshun He,
  • Sibo Fan,
  • Guangsong Su,
  • Xueyuan Zhao,
  • Zhenhao Zhao,
  • Yingjie Song,
  • Shupeng Sun,
  • Peng Li,
  • Zhongfang Zhao,
  • Jiandang Shi,
  • Wange Lu,
  • Lei Zhang

DOI
https://doi.org/10.1038/s41419-023-06392-w
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 13

Abstract

Read online

Abstract 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.