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bioRxiv · 10.1101/2020.11.03.367268

Long-range gene regulation network of the MGMT enhancer in modulating glioma cell sensitivity to temozolomide

He, A.·Chen, B.·Bi, J.·Wang, W.·Chen, J.·Qian, Y.·Shi, T.·Zhao, Z.·Shi, J.·Yang, H.·Zhang, L.·Lu, W.
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Abstract

Acquired resistance to temozolomide (TMZ) is a major obstacle in glioblastoma treatment. MGMT, a DNA repair protein, and the methylation at its gene promoter, plays an important role in TMZ resistance. However, some evidences have suggested a MGMT-independent mechanisms underlying TMZ resistance. Here, we used MGMT enhancer as a model and discovered that its deletion in glioma cells of low MGMT expression induced increased sensitivity to temozolomide. Analysis of a combination of RNA-seq and Capture Hi-C further suggested multiple long-range target genes regulated by the MGMT enhancer and that interactions may play important roles in glioma cell sensitivity to TMZ. This study reveals a novel mechanism of regulation of TMZ sensitivity in glioma cells.

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He, A., Chen, B., Bi, J., Wang, W., Chen, J., Qian, Y., Shi, T., Zhao, Z., Shi, J., Yang, H., Zhang, L., Lu, W.. 2020-11-04. Long-range gene regulation network of the MGMT enhancer in modulating glioma cell sensitivity to temozolomide. https://doi.org/10.1101/2020.11.03.367268

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