PARP1
生物钟
生物
癌变
癌症研究
昼夜节律
基因沉默
乳腺癌
时钟
每2
癌基因
癌症
遗传学
细胞周期
聚ADP核糖聚合酶
基因
聚合酶
内分泌学
作者
Tianshu Yang,Wei Huang,Tianyu Ma,Xin Yin,Jingyao Zhang,Miaomiao Huo,Ting Hu,Tianyang Gao,Wei Liu,Die Zhang,Hefen Yu,Xu Teng,Min Zhang,Hao Qin,Yunkai Yang,Baowen Yuan,Yan Wang
标识
DOI:10.1002/advs.202202737
摘要
Circadian rhythms, as physiological systems with self-regulatory functions in living organisms, are controlled by core clock genes and are involved in tumor development. The protein arginine methyltransferase 6 (PRMT6) serves as an oncogene in a myriad of solid tumors, including breast cancer. Hence, the primary aim of the current study is to investigate the molecular mechanisms by which the PRMT6 complex promotes breast cancer progression. The results show that PRMT6, poly(ADP-ribose) polymerase 1 (PARP1), and the cullin 4 B (CUL4B)-Ring E3 ligase (CRL4B) complex interact to form a transcription-repressive complex that co-occupies the core clock gene PER3 promoter. Moreover, genome-wide analysis of PRMT6/PARP1/CUL4B targets identifies a cohort of genes that is principally involved in circadian rhythms. This transcriptional-repression complex promotes the proliferation and metastasis of breast cancer by interfering with circadian rhythm oscillation. Meanwhile, the PARP1 inhibitor Olaparib enhances clock gene expression, thus, reducing breast carcinogenesis, indicating that PARP1 inhibitors have potential antitumor effects in high-PRMT6 expression breast cancer.
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