Circadian variation in MGMT promoter methylation and expression predicts sensitivity to temozolomide in glioblastoma.

ABSTRACT:

Purpose

Recent studies show that glioblastoma (GBM) is more sensitive to temozolomide (TMZ) in the morning. In cells, inhibiting O6-Methylguanine-DNA-Methyltransferase (MGMT) abolished time-dependent TMZ efficacy, suggesting that circadian regulation of this DNA repair enzyme underlies daily TMZ sensitivity. Here, we tested the hypotheses that MGMT promoter methylation and protein abundance vary with time-of-day in GBM, resulting in daily rhythms in TMZ efficacy.

Methods

We assessed daily rhythms in MGMT promoter methylation in GBM in vitro and retrospectively analyzed MGMT methylation status in human GBM biopsies collected at different times of day. Next, we measured MGMT and BMAL1 protein abundances in GBM cells collected at four-hour intervals. To understand the therapeut

SUBMITTER: Gonzalez-Aponte MF 

PROVIDER: S-EPMC12546296 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature