Abstract
Simple SummaryIn this manuscript we review the recent literature supporting a biological link between circadian clock disruption and thyroid cancer development and progression. After a brief description of the involvement of the circadian clock machinery in the cell cycle, stemness and cancer, we discuss the scientific evidence supporting the contribution of circadian clockwork dysfunction in thyroid tumorigenesis and the possible molecular mechanisms underlying this relationship. We also point out the potential clinical implications of this link highlighting its impact on thyroid cancer prevention, diagnosis and therapy.Thyroid cancer (TC) represents the most common malignancy of the endocrine system, with an increased incidence across continents attributable to both improvement of diagnostic procedures and environmental factors. Among the modifiable risk factors, insulin resistance might influence the development of TC. A relationship between circadian clock machinery disfunction and TC has recently been proposed. The circadian clock machinery comprises a set of rhythmically expressed genes responsible for circadian rhythms. Perturbation of this system contributes to the development of pathological states such as cancer. Several clock genes have been found deregulated upon thyroid nodule malignant transformation. The molecular mechanisms linking circadian clock disruption and TC are still unknown but could include insulin resistance. Circadian misalignment occurring during shift work, jet lag, high fat food intake, is associated with increased insulin resistance. This metabolic alteration, in turn, is associated with a well-known risk factor for TC i.e., hyperthyrotropinemia, which could also be induced by sleep disturbances. In this review, we describe the mechanisms controlling the circadian clock function and its involvement in the cell cycle, stemness and cancer. Moreover, we discuss the evidence supporting the link between circadian clockwork disruption and TC development/progression, highlighting its potential implications for TC prevention, diagnosis and therapy.
Highlights
Thyroid cancer (TC) represents the most common endocrine malignancy, which has shown a strikingly increasing incidence over the past few decades [1,2]
All these findings suggest that the PER2 gene exerts a potential role in regulating stemness, self-renewal, cell growth, cell cycle distribution, migration and invasion of GCS in glioma and are consistent with similar results obtained in colon cancer stem-like cells (CCSCs)
In line with these data, another study reported an altered expression of REV-ERBα and RORα genes in papillary TC (PTC) especially in those positive for BRAF-mutation [242]. Overall these results suggest that circadian clock characteristics are altered upon thyroid nodule malignant transformation/progression and that changes in clock gene expression profiles may be potentially employed in clinics as potential biomarkers for follicular TC (FTC) and disease progression (Figure 2)
Summary
Thyroid cancer (TC) represents the most common endocrine malignancy, which has shown a strikingly increasing incidence over the past few decades [1,2]. Among the potential modifiable risk factors of TC, particular attention has been paid to insulin resistance and hyperinsulinemia [4] These metabolic alterations have been rapidly increasing worldwide due to lifestyle modifications, which may include circadian clock disruption. At present, it is not completely clear how insulin resistance and related metabolic disorders may affect well-known molecular pathways involved in the pathogenesis of TC such as MAPK, PI3K/PTEN/AKT, TSH-R, and mTOR/p70S6K. The molecular mechanisms linking circadian clock disruption and TC are still unknown but could be, at least in part, insulin resistance This metabolic alteration is associated with a well-known risk factor for TC i.e., hyperthyrotropinemia [18,19,20] which, in turn, has been associated to sleep disturbances [21]. The scientific evidence supporting the possible biological link between the disruption of circadian clockwork and TC development/progression and its potential role for the TC prevention and treatment will be discussed
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