RNA editing has emerged as a novel mechanism in cancer progression. The double stranded RNA-specific adenosine deaminase (ADAR) modifies the expression of an important proportion of genes involved in cell cycle control, DNA damage response (DDR) and transcriptional processing, suggesting an important role of ADAR in transcriptome regulation. Despite the phenotypic implications of ADAR deregulation in several cancer models, the role of ADAR on DDR and proliferation in breast cancer has not been fully addressed. Here, we show that ADAR expression correlates significantly with clinical outcomes and DDR, cell cycle and proliferation mRNAs of previously reported edited transcripts in breast cancer patients. ADAR's knock-down in a breast cancer cell line produces stability changes of mRNAs involved in DDR and DNA replication. Breast cancer cells with reduced levels of ADAR show a decreased viability and an increase in apoptosis, displaying a significant decrease of their DDR activation, compared to control cells. These results suggest that ADAR plays an important role in breast cancer progression through the regulation of mRNA stability and expression of those genes involved in proliferation and DDR impacting the viability of breast cancer cells.

RNA编辑已成为癌症进展中的一种新机制。双链RNA特异性腺苷脱氨酶（ADAR）修饰了参与细胞周期控制，DNA损伤反应（DDR）和转录过程的重要基因表达，暗示了ADAR在转录组调控中的重要作用。尽管在几种癌症模型中ADAR失控具有表型意义，但尚未完全解决ADAR对DDR和乳腺癌扩散的作用。在这里，我们表明，ADAR表达与乳腺癌患者的临床结局，DDR，细胞周期和先前报道的已编辑转录本的增殖mRNA密切相关。乳腺癌细胞系中ADAR的敲低产生了与DDR和DNA复制有关的mRNA的稳定性变化。与对照细胞相比，具有降低的ADAR水平的乳腺癌细胞显示出活力降低和凋亡增加，显示出其DDR激活显着降低。这些结果表明，ADAR通过调节mRNA的稳定性以及参与增殖和DDR的基因表达来影响乳腺癌细胞的生存，从而在乳腺癌的发展中起重要作用。