Delactylation of H3K9 by Sirtuin6 inhibits MGMT transcription and reverses temozolomide resistance in glioblastoma

Nuclear SIRT6 deficiency is identified as a hallmark of temozolomide-resistant glioblastoma.

• Over 50% of glioblastoma patients exhibit resistance to temozolomide.
• Enhancing nuclear SIRT6 expression may resensitize TMZ-resistant glioblastoma cells to treatment.
• Combining the SIRT6 agonist MDL-800 with TMZ significantly inhibited cell growth and induced cell death in resistant glioblastoma both in lab tests and animal models.
• SIRT6 may inhibit the gene MGMT by reducing a specific modification on histone proteins, affecting how genes are expressed.
• The effectiveness of temozolomide treatment may improve through the nuclear movement of SIRT6, targeting the SIRT6-H3K9la-MGMT pathway.

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