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Can a disrupted sleep cycle increase your risk of lung cancer?

Researchers showed a cancer-signature gene is activated in mice with chronic jet lag, causing faster tumor growth in their lungs.

Image Credit: Photo by Kinga Howard on Unsplash

Do you have a disrupted sleep schedule? The internal clock that sets your body’s natural sleep and wake cycle is called your circadian rhythm. Your sleep schedule is considered disrupted when the time you sleep doesn’t match your circadian rhythm. Scientists have discovered that chronic disruptions in circadian rhythm increase the risk of cancer.            

Researchers have found the lungs in particular are affected by changes in circadian rhythm, so the risk of lung cancer increases in people who experience chronic disruptions in circadian rhythm. Scientists have shown changes in this natural cycle can decrease immunity, consequently leading to lung disease and cancer. However, they don’t fully understand how disrupted circadian rhythms cause lung cancer.

Scientists recently used mice to study how chronic circadian rhythm disruption impacts lung tumor formation. The scientists genetically engineered the mice by subjecting them to one of two treatments, each of which caused a different type of lung cancer. 

Genes that can cause cancer are called oncogenes. Genes that can prevent the growth of cancerous tumors are called active tumor suppressor genes. When someone has cancer, their oncogenes are turned on and their tumor suppressor genes are turned off. The scientists activated an oncogene mutation that led to lung cancer in all of the mice. They also deactivated a tumor suppressor gene in half of the mice.

The scientists changed the mice’s genes by giving them a special kind of protein, called an enzyme. This specific enzyme either removed an anti-cancer gene to produce an oncogene mutation, or changed the DNA to make less of a tumor suppressor gene. As a result, the scientists created two groups of genetically engineered mice with lung cancer, the second with a more aggressive cancer than the first. 

The scientists conducted an 8-week study where they exposed half the mice, including some with each kind of lung cancer, to a natural circadian rhythm with 12 hours of light followed by 12 hours of dark every day. The scientists exposed the other half to the same cycle, except every few days the light hours started 8 hours later. This treatment, referred to as the chronic jet lag treatment, models a disrupted circadian rhythm, similar to what a shift worker might experience. 

After 8 weeks, the scientists collected tissue samples from the mice every 4 hours for 24 hours to look for the development of cancer cells and molecules that control the circadian clock machinery. Taking samples every four hours allowed the scientists to look for any pattern associated with a disrupted circadian rhythm. 

In the mice subjected to the jet lag treatment, the scientists measured a disruption in some of the genes controlled by the circadian clock. However, they found no effect on specific proteins that sometimes regulate the circadian clock and control cancer cell growth. They also found jet lagged mice with the more aggressive form of lung cancer did not have increased tumor growth, but mice with the less aggressive form did. In comparison, the scientists found no genetic disruption and less tumor growth in the mice with normal circadian rhythms. 

The researchers found the jet lagged mice had increased activity of a protein known as a cancer-signature gene. Scientists have shown that triggering this protein can lead to tumor formation, but when this protein is inhibited, the growth of lung cancer cells is also inhibited. This pattern suggests the cancer-signature protein is necessary for lung cancer cells to grow. Since the jet lagged mice had more of this protein, the scientists suggested they would be more likely to develop tumors. 

Since chronic disruptions to circadian rhythms are common in people who travel extensively or do shift work, researchers want to understand the correlation between lung cancer and disrupted circadian rhythms. These scientists suggested future work should develop the cancer-signature protein as a potential target for tumor-preventing drug treatments.

Study Information

Original study: Circadian disruption enhances HSF1 signaling and tumorigenesis in Kras-driven lung cancer

Study was published on: September 28, 2022

Study author(s): Marie Pariollaud, Lara H. Ibrahim, Emanuel Irizarry, Rebecca M. Mello, Alanna B. Chan, Brian J. Altman, Reuben J. Shaw, Michael J. Bollong, R. Luke Wiseman, Katja A. Lamia

The study was done at: Scripps Research Institution (USA), University of Rochester Medical Center (USA)

The study was funded by: National Institute of Health, Brown Foundation for Cancer Research, National Science Foundation

Raw data availability: The RNA sequencing data is in the Gene Expression Omnibus with the accession number GSE194097.

Featured image credit: Photo by Kinga Howard on Unsplash

This summary was edited by: Melisa Yashinski