The PRMT6/PARP1/CRL4B Complex Regulates the Circadian Clock and Promotes Breast Tumorigenesis

Yang, Tianshu; Huang, Wei; Ma, Tianyu; Yin, Xin; Zhang, Jingyao; Huo, Miaomiao; Hu, Ting; Gao, Tianshu; Liu, Wei; Zhang, Die; Yu, Hefen; Teng, Xu; Zhang, Min; Qin, Hao; Yang, Yunkai; Yuan, Baowen; Wang, Yan

doi:10.1002/advs.202202737

Cited by 11 publications

(2 citation statements)

References 34 publications

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“…The role of protein arginine methyltransferase 6 (PRMT6) and poly ADP-ribose polymerase 1 (PARP1) in BC progression and their involvement in circadian rhythm disruption have been recently examined[ 104 ]. PRMT6 binds to PARP1, leading to the recruitment of the Cullin4B-Ring E3 Ligase (CRL4B) complex.…”

Section: Circadian Disruption and Clock Genes In Endocrine Tumorsmentioning

confidence: 99%

“…Inhibition of PARP1 enzymatic activity by olaparib disrupts the assembly of the PRMT6/PARP1/CRL4B complex, impacting circadian clock oscillation. As a result, PRMT6 and PARP1 inhibitors are suggested as potential treatments to restore natural circadian rhythms and obstruct tumor progression in BC cells with upregulated PRMT6 expression[ 104 ].…”

Section: Circadian Disruption and Clock Genes In Endocrine Tumorsmentioning

confidence: 99%

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Circadian rhythm disruption and endocrine-related tumors

Savvidis,

Kallistrou,

Kouroglou

et al. 2024

World J Clin Oncol

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This review delved into the intricate relationship between circadian clocks and physiological processes, emphasizing their critical role in maintaining homeostasis. Orchestrated by interlocked clock genes, the circadian timekeeping system regulates fundamental processes like the sleep-wake cycle, energy metabolism, immune function, and cell proliferation. The central oscillator in the hypothalamic suprachiasmatic nucleus synchronizes with light-dark cycles, while peripheral tissue clocks are influenced by cues such as feeding times. Circadian disruption, linked to modern lifestyle factors like night shift work, correlates with adverse health outcomes, including metabolic syndrome, cardiovascular diseases, infections, and cancer. We explored the molecular mechanisms of circadian clock genes and their impact on metabolic disorders and cancer pathogenesis. Specific associations between circadian disruption and endocrine tumors, spanning breast, ovarian, testicular, prostate, thyroid, pituitary, and adrenal gland cancers, are highlighted. Shift work is associated with increased breast cancer risk, with PER genes influencing tumor progression and drug resistance. CLOCK gene expression correlates with cisplatin resistance in ovarian cancer, while factors like aging and intermittent fasting affect prostate cancer. Our review underscored the intricate interplay between circadian rhythms and cancer, involving the regulation of the cell cycle, DNA repair, metabolism, immune function, and the tumor microenvironment. We advocated for integrating biological timing into clinical considerations for personalized healthcare, proposing that understanding these connections could lead to novel therapeutic approaches. Evidence supports circadian rhythm-focused therapies, particularly chronotherapy, for treating endocrine tumors. Our review called for further research to uncover detailed connections between circadian clocks and cancer, providing essential insights for targeted treatments. We emphasized the importance of public health interventions to mitigate lifestyle-related circadian disruptions and underscored the critical role of circadian rhythms in disease mechanisms and therapeutic interventions.

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Section: Circadian Disruption and Clock Genes In Endocrine Tumorsmentioning

confidence: 99%

Section: Circadian Disruption and Clock Genes In Endocrine Tumorsmentioning

confidence: 99%

Circadian rhythm disruption and endocrine-related tumors

Savvidis,

Kallistrou,

Kouroglou

et al. 2024

World J Clin Oncol

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The PRMT6/PARP1/CRL4B Complex Regulates the Circadian Clock and Promotes Breast Tumorigenesis

Yang

Huang

et al. 2023

Advanced Science

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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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