HDAC8 affects MGMT levels in glioblastoma cell lines via interaction with the proteasome receptor ADRM1.

ABSTRACT: Temozolomide (TMZ) is an alkylating agent chemotherapy drug used as a first-line treatment for glioblastoma multiforme (GBM). O⁶-methyl-guanine DNA methyltransferase (MGMT) repairs DNA damage induced by TMZ; hence, elevated MGMT levels usually correlate with TMZ resistance. MGMT promoter methylation is a key regulatory mechanism for MGMT expression and is important in overcoming TMZ therapy resistance. To date, little is known about how MGMT expression is regulated beyond promoter methylation. In this work, we show an alternative mechanism by which MGMT levels are regulated independent of its promoter methylation status. We found that inhibition of the histone deacetylase HDAC8 by either HDAC8-specific inhibitor PCI34051 or HDAC8 shRNA decreases MGMT levels in GBM cell lines. Fu

SUBMITTER: Santos-Barriopedro I 

PROVIDER: S-EPMC6872666 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature