Advertisement

 

 

Remote reprogramming of hepatic circadian transcriptome by breast cancer.

Remote reprogramming of hepatic circadian transcriptome by breast cancer.
Author Information (click to view)

Hojo H, Enya S, Arai M, Suzuki Y, Nojiri T, Kangawa K, Koyama S, Kawaoka S,


Hojo H, Enya S, Arai M, Suzuki Y, Nojiri T, Kangawa K, Koyama S, Kawaoka S, (click to view)

Hojo H, Enya S, Arai M, Suzuki Y, Nojiri T, Kangawa K, Koyama S, Kawaoka S,

Advertisement

Oncotarget 2017 04 06() doi 10.18632/oncotarget.16699

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.

Submit a Comment

Your email address will not be published. Required fields are marked *

19 − seventeen =

[ HIDE/SHOW ]