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Remote reprogramming of hepatic circadian transcriptome by breast cancer.

ABSTRACT: Cancers adversely affect organismal physiology. To date, the genes within a patient responsible for systemically spreading cancer-induced physiological disruption remain elusive. To identify host genes responsible for transmitting disruptive, cancer-driven signals, we thoroughly analyzed the transcriptome of a suite of host organs from mice bearing 4T1 breast cancer, and discovered complexly rewired patterns of circadian gene expression in the liver. Our data revealed that 7 core clock transcription factors, represented by Rev-erba and Rorg, exhibited abnormal daily expression rhythm in the liver of 4T1-bearing mice. Accordingly, expression patterns of specific set of downstream circadian genes were compromised. Osgin1, a marker for oxidative stress, was an example. Specific downstream genes, including E2f8, a transcriptional repressor that controls cellular polyploidy, displayed a striking pattern of disruption, "day-night reversal." Meanwhile, we found that the liver of 4T1-bearing mice suffered from increased oxidative stress. The tetraploid hepatocytes population was concomitantly increased in 4T1-bearing mice, which has not been previously appreciated as a cancer-induced phenotype. In summary, the current study provides a comprehensive characterization of the 4T1-affected hepatic circadian transcriptome that possibly underlies cancer-induced physiological alteration in the liver.

SUBMITTER: Hojo H

PROVIDER: S-EPMC5470956 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Remote reprogramming of hepatic circadian transcriptome by breast cancer.

Hojo Hiroaki H Enya Sora S Arai Miki M Suzuki Yutaka Y Nojiri Takashi T Kangawa Kenji K Koyama Shinsuke S Kawaoka Shinpei S

Oncotarget 20170501 21

Cancers adversely affect organismal physiology. To date, the genes within a patient responsible for systemically spreading cancer-induced physiological disruption remain elusive. To identify host genes responsible for transmitting disruptive, cancer-driven signals, we thoroughly analyzed the transcriptome of a suite of host organs from mice bearing 4T1 breast cancer, and discovered complexly rewired patterns of circadian gene expression in the liver. Our data revealed that 7 core clock transcrip ...[more]

PMID: 28388556

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Remote reprogramming of hepatic circadian transcriptome by breast cancer.

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Remote reprogramming of hepatic circadian transcriptome by breast cancer.

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