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

Cell Death Dis. 2024 Jan 4;15(1):6. doi: 10.1038/s41419-023-06392-w.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Alkylating / pharmacology
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Drug Resistance, Neoplasm / genetics
  • Enhancer RNAs
  • Glioma* / drug therapy
  • Glioma* / genetics
  • Glioma* / metabolism
  • Humans
  • MicroRNAs* / genetics
  • Temozolomide / pharmacology
  • Temozolomide / therapeutic use

Substances

  • Temozolomide
  • Enhancer RNAs
  • MicroRNAs
  • Antineoplastic Agents, Alkylating