PRMT5 regulates RNA m6A demethylation for doxorubicin sensitivity in breast cancer

• DOI: 10.1016/j.ymthe.2022.03.003
• Publication Date: 2022-03-10T02:18:22Z
• Authors: Ying Wu; Zhe Wang; Lu Han; Zhihao Guo; Bohua Yan; Lili Guo; Huadong Zhao; Mengying Wei; Niuniu Hou; Jing Ye; Zhe Wang; Changhong Shi; Suling Liu; Ceshi Chen; Suning Chen; Ting Wang; Jun Yi; JianPing Zhou; Libo Yao; Wenxia Zhou; Rui Ling; Jian Zhang
• Keywords: Demethylase

Cancer cells respond to various stressful conditions through the dynamic regulation of RNA m6A modification. Doxorubicin is a widely used chemotherapeutic drug that induces DNA damage. It interesting know whether cancer regulate damage response and doxorubicin sensitivity Here, we found treatment significantly induced methylation in breast both dose- time-dependent manner. However, protein arginine methyltransferase 5 (PRMT5) inhibited modification under by enhancing nuclear translocation demethylase AlkB homolog (ALKBH5), which was previously believed be exclusively localized nucleus. Then, ALKBH5 removed BRCA1 for mRNA stabilization further enhanced repair competency decrease efficacy cells. Importantly, identified approved tadalafil as novel PRMT5 inhibitor could increase cancer. The strategy targeting with promising approach promote regulation.