TERT upstream promoter methylation regulates TERT expression and acts as a therapeutic target in TERT promoter mutation-negative thyroid cancer.

ABSTRACT:

Background

DNA hypermethylation and hotspot mutations were frequently observed in the upstream and core promoter of telomerase reverse transcriptase (TERT), respectively, and they were associated with increased TERT expression and adverse clinical outcomes in thyroid cancer. In TERT promoter mutant cancer cells, the hypomethylated TERT mutant allele was active and the hypermethylated TERT wild-type allele was silenced. However, whether and how the upstream promoter methylation regulates TERT expression in TERT mutation-negative cells were largely unknown.

Methods

DNA demethylating agents 5-azacytidine and decitabine and a genomic locus-specific demethylation system based on dCas9-TET1 were used to assess the effects of TERT upstream promoter methylation on TERT expression, c

SUBMITTER: Li S 

PROVIDER: S-EPMC11297792 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature