Mazzoccoli Gianluigi, Vinciguerra Manlio, Papa Gennaro, Piepoli Ada
Gianluigi Mazzoccoli, Manlio Vinciguerra, Department of Medical Sciences, Division of Internal Medicine and Chronobiology Unit, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", 71013 San Giovanni Rotondo Foggia, Italy.
World J Gastroenterol. 2014 Apr 21;20(15):4197-207. doi: 10.3748/wjg.v20.i15.4197.
Colorectal cancer is the most prevalent among digestive system cancers. Carcinogenesis relies on disrupted control of cellular processes, such as metabolism, proliferation, DNA damage recognition and repair, and apoptosis. Cell, tissue, organ and body physiology is characterized by periodic fluctuations driven by biological clocks operating through the clock gene machinery. Dysfunction of molecular clockworks and cellular oscillators is involved in tumorigenesis, and altered expression of clock genes has been found in cancer patients. Epidemiological studies have shown that circadian disruption, that is, alteration of bodily temporal organization, is a cancer risk factor, and an increased incidence of colorectal neoplastic disease is reported in shift workers. In this review we describe the involvement of the circadian clock circuitry in colorectal carcinogenesis and the therapeutic strategies addressing temporal deregulation in colorectal cancer.
结直肠癌是消化系统癌症中最常见的。癌症发生依赖于细胞过程的调控紊乱,如新陈代谢、增殖、DNA损伤识别与修复以及细胞凋亡。细胞、组织、器官和身体的生理学特征是由通过时钟基因机制运行的生物钟驱动的周期性波动。分子生物钟和细胞振荡器的功能障碍与肿瘤发生有关,并且在癌症患者中发现了时钟基因的表达改变。流行病学研究表明,昼夜节律紊乱,即身体时间组织的改变,是一种癌症风险因素,并且据报道轮班工作者患结直肠肿瘤性疾病的发病率增加。在这篇综述中,我们描述了昼夜节律时钟电路在结直肠癌发生中的作用以及针对结直肠癌时间失调的治疗策略。