Computational Analyses Reveal Deregulated Clock Genes Associated with Breast Cancer Development in Night Shift...

Area of Science:

• Oncology
• Chronobiology
• Molecular Biology

Background:

• Breast cancer (BC) is a leading cause of cancer death in women globally.
• Night shift work (NSW) is associated with increased BC risk, potentially due to circadian rhythm disruption.
• The molecular mechanisms linking NSW to BC risk remain unclear.

Purpose of the Study:

• To investigate clock genes as potential biomarkers for BC in women exposed to long-term NSW.
• To identify molecular mechanisms, including post-transcriptional regulation by miRNAs, influenced by NSW.

Main Methods:

• Analysis of clock gene expression in paired breast cancer and normal tissues from Nurses' Health Studies.
• Validation using additional gene expression datasets and single-cell sequencing data.
• Identification of miRNA regulators of clock genes.

Main Results:

• Significant alterations in clock gene expression were observed in BC tissues compared to normal tissues.
• Specific clock genes (BHLHE40, CIART, CLOCK, PDPK1, TIMELESS) were over-expressed, while others (HLF, NFIL3, NPAS3, PER1, PER3, SIM1, TEF) were under-expressed.
• Downregulation of PER1/TEF and upregulation of CLOCK correlated with increased BC risk; 26 miRNAs were identified as potential NSW-influenced regulators.

Conclusions:

• A panel of clock genes and circadian miRNAs are proposed as BC susceptibility biomarkers for night shift workers.
• These findings support potential applications in risk stratification and early BC detection strategies for this population.