Hassan Azka, Ahmad Jamil, Ashraf Hufsah, Ali Amjad
Research Center for Modeling and Simulation (RCMS), National University of Scinces and Technology (NUST), Islamabad, Pakistan.
Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Science and Technology, Islamabad, Pakistan.
PeerJ. 2018 Jun 6;6:e4877. doi: 10.7717/peerj.4877. eCollection 2018.
Circadian rhythms maintain a 24 h oscillation pattern in metabolic, physiological and behavioral processes in all living organisms. Circadian rhythms are organized as biochemical networks located in hypothalamus and peripheral tissues. Rhythmicity in the expression of circadian clock genes plays a vital role in regulating the process of cell division and DNA damage control. The oncogenic protein, MYC and the tumor suppressor, p53 are directly influenced by the circadian clock. Jet lag and altered sleep/wake schedules prominently affect the expression of molecular clock genes. This study is focused on developing a Petri net model to analyze the impacts of long term jet lag on the circadian clock and its probable role in tumor progression. The results depict that jet lag disrupts the normal rhythmic behavior and expression of the circadian clock proteins. This disruption leads to persistent expression of MYC and suppressed expression of p53. Thus, it is inferred that jet lag altered circadian clock negatively affects the expressions of cell cycle regulatory genes and contribute in uncontrolled proliferation of tumor cells.
昼夜节律在所有生物体的代谢、生理和行为过程中维持24小时振荡模式。昼夜节律被组织成位于下丘脑和外周组织中的生化网络。昼夜节律时钟基因表达的节律性在调节细胞分裂和DNA损伤控制过程中起着至关重要的作用。致癌蛋白MYC和肿瘤抑制因子p53直接受昼夜节律时钟影响。时差反应和改变的睡眠/觉醒时间表显著影响分子时钟基因的表达。本研究的重点是开发一个Petri网模型，以分析长期时差反应对昼夜节律时钟的影响及其在肿瘤进展中的可能作用。结果表明，时差反应会破坏昼夜节律时钟蛋白的正常节律行为和表达。这种破坏导致MYC的持续表达和p53的表达受到抑制。因此，推断时差反应改变的昼夜节律时钟对细胞周期调节基因的表达产生负面影响，并导致肿瘤细胞的不受控制增殖。
