Targeting CDK9-dependent transcriptional addiction: a novel chemoprevention strategy for oral carcinogenesis via adenosine deaminase modulation.

ABSTRACT: Oncogenic dysregulation of transcription can entail defective control of gene expression and drive tumor initiation. This addiction to certain transcriptional programs provides opportunities to prevent carcinogenesis, and targeting transcriptional cyclin-dependent kinases (tCDKs) holds promise to show clinical benefit. Here, we firstly reported that transcriptional addiction existed in the process of oral mucosal carcinogenesis and high expression of CDK9 contributed to transcriptional dysregulation. CDK9 inhibition paused RNA Pol II transcription cycle to induce cell apoptosis in vitro and in vivo, effectively hampering carcinogenesis in 4-NQO-induced mouse models. Mechanically, targeting CDK9 decreased adenosine deaminase (ADA) expression and suppressed ADA activity, impacting on the enz

SUBMITTER: Zeng Q 

PROVIDER: S-EPMC12686051 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature