Circadian clock characteristics are altered in human thyroid malignant nodules

Area of Science:

• Chronobiology
• Molecular Oncology
• Endocrinology

Background:

• The circadian clock, the body's internal timekeeper, influences numerous physiological processes.
• Dysregulation of clock gene expression is increasingly linked to various human cancers.
• Emerging evidence connects the circadian oscillator, cell cycle, and oncogenic transformation.

Purpose of the Study:

• To characterize the molecular details of the circadian clockwork in human thyroid nodules.
• To investigate alterations in clock gene expression in benign versus malignant thyroid tissues.
• To explore the relationship between circadian rhythm disruption and thyroid oncogenesis.

Main Methods:

• Quantitative RT-PCR was used to assess clock transcript levels in thyroid tissue samples.
• Primary thyrocytes from normal, benign, and malignant thyroid tissues were cultured in vitro.
• Circadian bioluminescence reporter assays and quantitative RT-PCR analyzed clock gene expression after synchronization.

Main Results:

• Bmal1 expression was upregulated, and Cry2 was downregulated in follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma (PTC) compared to normal and benign tissues.
• Normal and benign thyroid cells exhibited robust circadian oscillations in clock gene expression.
• Thyrocytes from FTC and PTC showed similar oscillations, except for altered Per2 in PTC; poorly differentiated carcinoma cells displayed disrupted circadian oscillations.

Conclusions:

• This study provides the first molecular characterization of the human thyroid circadian clock.
• Alterations in thyroid clock machinery correlate with malignant transformation, offering insights into cancer development.
• Understanding these circadian clock disruptions may enhance preoperative diagnostics for thyroid nodules.