抗辐射性
DNA修复
癌症研究
DNA损伤
乳腺癌
基因敲除
生物
奥拉帕尼
E2F型
癌症
癌症干细胞
干细胞
顺铂
细胞周期
聚ADP核糖聚合酶
细胞生物学
DNA
细胞培养
化疗
遗传学
聚合酶
作者
Luqing Wei,Yu Bai,Na Lei,Yu Sun,Chenghai Zhao,Wei Wang
标识
DOI:10.1016/j.bbadis.2023.166816
摘要
Therapy resistance is a major hurdle to the treatment of human malignant tumors. Both DNA damage repair and stem-like properties contribute to chemoresistance and radioresistance. E2F transcription factor 3 (E2F3) is overexpressed in breast cancer tissues, and promotes proliferation of breast cancer cells. Higher E2F3 level is associated with shorter survival of breast cancer patients. Functional studies further showed that E2F3 promotes S-phage entry, DNA replication, DNA damage repair and stem-like properties. Accordingly, E2F3 knockdown sensitizes breast cancer cells to DNA-damaging agents Adriamycin, Cisplatin, Olaparib and X-ray. Forkhead box M1 (FOXM1) is a downstream molecule of E2F3 signaling, mediating the effects of E2F3 on breast cancer cells. In an m6A methyltransferase METTL14-dependent manner, YTH RNA binding protein F2 (YTHDF2) increase E2F3 mRNA stability and expression, promotes DNA damage repair and induces therapy resistance. These data demonstrate that YTHDF2-E2F3 pathway is a novel target to overcome chemoresistance and radioresistance in breast cancer.
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