Beyond Sleep: How Circadian Rhythm Disruption Drives Cancer Progression

Two new studies reveal how circadian rhythm disruption promotes breast cancer and liver cancer progression through molecular mechanisms involving BMAL1, CLOCK, PER3, and lncRNA AC019080.1.

Updated May 9, 20262 min read

TL;DR

Circadian disruption dysregulates core clock genes BMAL1/CLOCK/PER3, activating PI3K-Akt pathways in breast cancer, while lncRNA AC019080.1 drives liver cancer through Wnt/beta-catenin signaling.

The Hidden Connection Between Your Body Clock and Cancer

We have known for decades that shift workers have higher rates of certain cancers. But only now are scientists beginning to untangle the molecular mechanisms behind this connection.

Study 1: Breast Cancer and the Broken Clock

Published in Bioinformation, researchers analyzed transcriptomic data from breast cancer cells (MCF-7) vs normal breast cells (MCF-10A). They identified 1,788 differentially expressed genes:

  • Core clock genes BMAL1, CLOCK, and PER3 showed disrupted expression patterns
  • PI3K-Akt signaling -- one of the most frequently activated pathways in cancer -- was significantly upregulated
  • Cell adhesion and apoptosis pathways were downregulated

Study 2: Circadian Clocks in Liver Cancer

Published in Open Life Sciences, researchers mapped 24 circadian rhythm-related mRNAs and 433 CRR long non-coding RNAs in hepatocellular carcinoma (HCC):

  • 46 prognostic CRR-lncRNAs were significantly upregulated in HCC
  • Three distinct molecular subtypes identified based on circadian gene expression
  • lncRNA AC019080.1 silencing inhibited proliferation, migration, and invasion while promoting apoptosis
  • Mechanism: Suppression of the Wnt/beta-catenin signaling pathway

Three Mechanisms Linking Circadian Disruption to Cancer

  1. Disrupted Cell Cycle Control: Circadian genes directly regulate cell cycle checkpoints
  2. Altered Immune Surveillance: Circadian gene expression predicts immune infiltration levels
  3. Metabolic Reprogramming: Circadian genes regulate glucose and lipid metabolism

What This Means for Sleep Health

These findings elevate sleep hygiene from a wellness recommendation to a potential cancer prevention strategy. Chronic circadian disruption leads to dysregulated clock genes, which promotes unchecked cell growth and cancer.


References

  1. Disrupted circadian control promotes oncogenesis in breast cancer. Bioinformation (2025). DOI: 10.6026/973206300214945 | PMID: 41908013
  2. Circadian rhythm-based prognostic features predict immune infiltration in molecular subtypes of hepatocellular carcinoma. Open Life Sciences (2025). DOI: 10.1515/biol-2025-1208 | PMID: 41883395

References

  1. [1]https://pubmed.ncbi.nlm.nih.gov/41908013/
  2. [2]https://pubmed.ncbi.nlm.nih.gov/41883395/

Related Topics