Affiliation:
1. Key Laboratory of Cancer and Microbiome State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100021 China
2. Beijing Key Laboratory of Cancer Invasion and Metastasis Research Department of Biochemistry and Molecular Biology School of Basic Medical Sciences Capital Medical University Beijing 100069 China
3. Key Laboratory of Immune Microenvironment and Disease (Ministry of Education) Department of Biochemistry and Molecular Biology School of Basic Medical Sciences Tianjin Medical University Tianjin 300070 China
Abstract
AbstractCircadian 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.
Funder
National Natural Science Foundation of China
Major State Basic Research Development Program of China
Subject
General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)
Cited by
4 articles.
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