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

Temozolomide (TMZ) resistance of glioma cells is currently a critical problem in glioma clinical treatment. In this study, we reveal a bivalent function of a super-enhancer RNA LINC02454 in modulating glioma cell sensitivity to TMZ via regulation of SORBS2 and DDR expression. LINC02454 increased TMZ sensitivity by maintaining 3D chromatin structure and promoting SORBS2 expression, but paradoxically decreased TMZ sensitivity by binding to the DDR1 locus and promoting DDR1 transcription. This study proposes a new regulatory mechanism governing glioma cell sensitivity to TMZ and provides new insights that may improve therapies against glioma. Overall design: 2 biological replicates were analyzed for U251 or U87 by RNA-seq in TMZ-treated cells for 72 h, 2 biological replicates were analyzed for LINC02454 SE KO cells, LINC02454 KD cells and LINC02454 OE cells by RNA-seq, 2 biological replicates of H3K27Ac ChIP-seq for U251 lines, 2 biological replicates were analyzed for U251 lines by Capture-C.