MiR-18a impairs DNA damage response through downregulation of ataxia telangiectasia mutated (ATM) kinase.

ABSTRACT: The DNA damage response (DDR) encompasses multi-step processes by which cells evolve to sense DNA damage, transduce the signal and initiate the repair of damaged DNA. Ataxia Telangiectasia Mutated (ATM) Kinase, which functions as the primary sensor and transducer of DNA damage signal, has been demonstrated to play an important role in the DDR and cancer prevention. Hence, understanding the molecular mechanisms underlying the regulation of ATM has received much attention. Here, we found that miR-18a was upregulated in both cell lines and patients' tissue samples of breast cancer. Furthermore, we demonstrated that ectopically expressing miR-18a downregulated ATM expression by directly targeting the ATM-3'-UTR and abrogated the IR-induced cell cycle arrest. Similar to the effect of ATM siRNA,

SUBMITTER: Song L 

PROVIDER: S-EPMC3181320 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature