Remote reprogramming of hepatic circadian transcriptome by breast cancer

Hiroaki Hojo, Sora Enya, Miki Arai, Yutaka Suzuki, Takashi Nojiri, Kenji Kangawa, Shinsuke Koyama, Shinpei Kawaoka

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)


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, cancerdriven 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-erbα and Rorγ, 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.

Original languageEnglish
Pages (from-to)34128-34140
Number of pages13
Issue number21
Publication statusPublished - 2017
Externally publishedYes


  • Breast cancer
  • Hepatic circadian transcriptome
  • Hepatic oxidative stress
  • Hepatic polyploidization
  • RNA-seq

ASJC Scopus subject areas

  • Oncology


Dive into the research topics of 'Remote reprogramming of hepatic circadian transcriptome by breast cancer'. Together they form a unique fingerprint.

Cite this