<i>N</i> ⁶-methyladenosine promotes temozolomide resistance through non-canonical regulation of mRNA stability in glioblastoma cells.

ABSTRACT: N ⁶-methyladenosine (m⁶A) is a critical regulator of mRNA processing and function, impacting nearly every step of the mRNA lifecycle. Changes in m⁶A status have been implicated in many different types of cancer, including glioblastoma where acquired resistance to temozolomide remains a major clinical challenge. We established glioblastoma cell culture models of acquired temozolomide resistance and analyzed the role of m⁶A in controlling resistance-associated pathways. We show that m⁶A stabilizes key genes and pathways promoting temozolomide resistance in glioblastoma, including MGMT, the enzyme that repairs primary temzolomide-induced DNA damage, and PI3K/Akt signaling, a major driver of chemoresistance. Pharmacological i

SUBMITTER: Dangelmaier EA 

PROVIDER: S-EPMC12458249 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature