Adeola Henry A, Papagerakis Silvana, Papagerakis Petros
Hair and Skin Research Laboratory, Division of Dermatology, Department of Medicine, Faculty of Health Sciences and Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa.
Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, University of the Western Cape and Tygerberg Hospital, Cape Town, South Africa.
Front Physiol. 2019 Apr 16;10:399. doi: 10.3389/fphys.2019.00399. eCollection 2019.
A vast majority of the pathophysiological and metabolic processes in humans are temporally controlled by a master circadian clock located centrally in the hypothalamic suprachiasmatic nucleus of the brain, as well as by specialized peripheral oscillators located in other body tissues. This circadian clock system generates a rhythmical diurnal transcriptional-translational cycle in clock genes and protein expression and activities regulating numerous downstream target genes. Clock genes as key regulators of physiological function and dysfunction of the circadian clock have been linked to various diseases and multiple morbidities. Emerging omics technologies permits largescale multi-dimensional investigations of the molecular landscape of a given disease and the comprehensive characterization of its underlying cellular components (e.g., proteins, genes, lipids, metabolites), their mechanism of actions, functional networks and regulatory systems. Ultimately, they can be used to better understand disease and interpatient heterogeneity, individual profile, identify personalized targetable key molecules and pathways, discover novel biomarkers and genetic alterations, which collectively can allow for a better patient stratification into clinically relevant subgroups to improve disease prediction and prevention, early diagnostic, clinical outcomes, therapeutic benefits, patient's quality of life and survival. The use of "omics" technologies has allowed for recent breakthroughs in several scientific domains, including in the field of circadian clock biology. Although studies have explored the role of clock genes using circadiOmics (which integrates circadian omics, such as genomics, transcriptomics, proteomics and metabolomics) in human disease, no such studies have investigated the implications of circadian disruption in oral, head and neck pathologies using multi-omics approaches and linking the omics data to patient-specific circadian profiles. There is a burgeoning body of evidence that circadian clock controls the development and homeostasis of oral and maxillofacial structures, such as salivary glands, teeth and oral epithelium. Hence, in the current era of precision medicine and dentistry and patient-centered health care, it is becoming evident that a multi-omics approach is needed to improve our understanding of the role of circadian clock-controlled key players in the regulation of head and neck pathologies. This review discusses current knowledge on the role of the circadian clock and the contribution of omics-based approaches toward a novel precision health era for diagnosing and treating head and neck pathologies, with an emphasis on oral, head and neck cancer and Sjögren's syndrome.
人类绝大多数病理生理和代谢过程受位于大脑下丘脑视交叉上核的主生物钟以及位于身体其他组织的特殊外周振荡器的时间控制。这种生物钟系统在生物钟基因中产生有节奏的昼夜转录-翻译循环以及调节众多下游靶基因的蛋白质表达和活性。生物钟基因作为生物钟生理功能和功能障碍的关键调节因子，已与各种疾病和多种发病率相关联。新兴的组学技术允许对特定疾病的分子景观进行大规模多维度研究，并对其潜在的细胞成分（如蛋白质、基因、脂质、代谢物）、其作用机制、功能网络和调节系统进行全面表征。最终，它们可用于更好地理解疾病和患者间的异质性、个体特征，识别个性化的可靶向关键分子和途径，发现新的生物标志物和基因改变，这些共同可使患者更好地分层为临床相关亚组，以改善疾病预测和预防、早期诊断、临床结果、治疗效益、患者生活质量和生存率。“组学”技术的应用在包括生物钟生物学领域在内的几个科学领域取得了近期突破。尽管已有研究利用昼夜节律组学（整合基因组学、转录组学、蛋白质组学和代谢组学等昼夜节律组学）探讨生物钟基因在人类疾病中的作用，但尚无此类研究使用多组学方法研究昼夜节律紊乱在口腔、头颈病理学中的影响，并将组学数据与患者特定的昼夜节律特征联系起来。越来越多的证据表明，生物钟控制着口腔颌面部结构（如唾液腺、牙齿和口腔上皮）的发育和稳态。因此，在当前精准医学和牙科以及以患者为中心的医疗保健时代，显然需要一种多组学方法来增进我们对生物钟控制的关键参与者在头颈病理学调节中的作用的理解。本综述讨论了关于生物钟作用的当前知识以及基于组学的方法对诊断和治疗头颈病理学的新型精准健康时代的贡献，重点是口腔、头颈癌和干燥综合征。
