Modeling and analysis of the impacts of jet lag on circadian rhythm and its role in tumor growth

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.

[1]  Denis Thieffry,et al.  Qualitative Petri Net Modelling of Genetic Networks , 2006, Trans. Comp. Sys. Biology.

[2]  M. Hughes,et al.  A circadian gene expression atlas in mammals: Implications for biology and medicine , 2014, Proceedings of the National Academy of Sciences.

[3]  Y Sakaki,et al.  Resetting central and peripheral circadian oscillators in transgenic rats. , 2000, Science.

[4]  L. Keith,et al.  Circadian rhythm chaos: a new breast cancer marker. , 2001, International journal of fertility and women's medicine.

[5]  Kathryn A. O’Donnell,et al.  The great MYC escape in tumorigenesis. , 2005, Cancer cell.

[6]  Adrien Richard,et al.  Delays in Biological Regulatory Networks (BRN) , 2006, International Conference on Computational Science.

[7]  B. Hoffman,et al.  Apoptotic signaling by c-MYC , 2008, Oncogene.

[8]  G. Evan,et al.  Proliferation, cell cycle and apoptosis in cancer , 2001, Nature.

[9]  Sobia Rana,et al.  Circadian rhythm and its role in malignancy , 2010, Journal of circadian rhythms.

[10]  D. Mirick,et al.  Circadian Disruption, Shift Work and the Risk of Cancer: A Summary of the Evidence and Studies in Seattle , 2006, Cancer Causes & Control.

[11]  Martin Schwarick,et al.  Snoopy - A Unifying Petri Net Tool , 2012, Petri Nets.

[12]  H. Kori,et al.  Accelerating recovery from jet lag: prediction from a multi-oscillator model and its experimental confirmation in model animals , 2017, Scientific Reports.

[13]  J. Comet,et al.  The SMBioNet Method for Discovering Models of Gene Regulatory Networks , 2009 .

[14]  T. Holford,et al.  Clock-cancer connection in non-Hodgkin's lymphoma: a genetic association study and pathway analysis of the circadian gene cryptochrome 2. , 2009, Cancer research.

[15]  X. Ao,et al.  The role of circadian rhythm in breast cancer. , 2013, Chinese journal of cancer research = Chung-kuo yen cheng yen chiu.

[16]  Adrien Richard,et al.  Application of formal methods to biological regulatory networks: extending Thomas' asynchronous logical approach with temporal logic. , 2004, Journal of theoretical biology.

[17]  Hidde de Jong,et al.  Modeling and Simulation of Genetic Regulatory Systems: A Literature Review , 2002, J. Comput. Biol..

[18]  M. Greene.  Circadian rhythms and tumor growth. , 2012, Cancer letters.

[19]  S. Kauffman.  Metabolic stability and epigenesis in randomly constructed genetic nets. , 1969, Journal of theoretical biology.

[20]  Michelle Girvan,et al.  Resynchronization of circadian oscillators and the east-west asymmetry of jet-lag. , 2016, Chaos.

[21]  M. Henriksson,et al.  The Myc oncoprotein as a therapeutic target for human cancer. , 2006, Seminars in cancer biology.

[22]  Elizabeth A. Shephard,et al.  Cell Biology: A Short Course , 2003 .

[23]  G. Evan,et al.  Wnt signaling promotes oncogenic transformation by inhibiting c-Myc–induced apoptosis , 2002, The Journal of cell biology.

[24]  Hassane Alla,et al.  Discrete, continuous, and hybrid Petri Nets , 2004 .

[25]  Ping Zheng,et al.  The circadian clock gene Bmal1 acts as a potential anti-oncogene in pancreatic cancer by activating the p53 tumor suppressor pathway. , 2016, Cancer letters.

[26]  G. Eichele,et al.  The circadian rhythm of glucocorticoids is regulated by a gating mechanism residing in the adrenal cortical clock. , 2006, Cell metabolism.

[27]  Denis Thieffry,et al.  Qualitative modelling of regulated metabolic pathways: application to the tryptophan biosynthesis in E.Coli , 2005, ECCB/JBI.

[28]  P. Shaw,et al.  The role of p53 in cell cycle regulation. , 1996, Pathology, research and practice.

[29]  S H Strogatz,et al.  Human sleep and circadian rhythms: a simple model based on two coupled oscillators , 1987, Journal of mathematical biology.

[30]  D. Golombek,et al.  Physiology of circadian entrainment. , 2010, Physiological reviews.

[31]  Stefano Iacobelli,et al.  Effects of light and food schedules on liver and tumor molecular clocks in mice. , 2005, Journal of the National Cancer Institute.

[32]  Ethan D Buhr,et al.  Molecular components of the Mammalian circadian clock. , 2013, Handbook of experimental pharmacology.

[33]  Claudine Chaouiya,et al.  Petri net modelling of biological networks , 2007, Briefings Bioinform..

[34]  Hiroki Yokota,et al.  Application of Petri Nets in Bone Remodeling , 2009, Gene regulation and systems biology.

[35]  Paolo Sassone-Corsi,et al.  Metabolism and cancer: the circadian clock connection , 2009, Nature Reviews Cancer.

[36]  T. Holford,et al.  Non-synonymous polymorphisms in the circadian gene NPAS2 and breast cancer risk , 2008, Breast Cancer Research and Treatment.

[37]  F. Scheer,et al.  Circadian disruption and SCN control of energy metabolism , 2011, FEBS letters.

[38]  S. Reppert,et al.  Coordination of circadian timing in mammals , 2002, Nature.

[39]  Samar Hayat Khan Tareen,et al.  Modelling and Analysis of the Feeding Regimen Induced Entrainment of Hepatocyte Circadian Oscillators Using Petri Nets , 2015, PloS one.

[40]  Monika Heiner,et al.  Modeling membrane systems using colored stochastic Petri nets , 2013, Natural Computing.

[41]  Achim Kramer,et al.  Tuning the Mammalian Circadian Clock: Robust Synergy of Two Loops , 2011, PLoS Comput. Biol..

[42]  P. Sassone-Corsi,et al.  The circadian clock and cell cycle: interconnected biological circuits. , 2013, Current opinion in cell biology.

[43]  U. Schibler,et al.  The mammalian circadian timing system: organization and coordination of central and peripheral clocks. , 2010, Annual review of physiology.

[44]  Michael Koutsilieris,et al.  Circadian Rhythm Disruption in Cancer Biology , 2012, Molecular medicine.

[45]  Christel Baier,et al.  Principles of model checking , 2008 .

[46]  R. Illner,et al.  A model for generating circadian rhythm by coupling ultradian oscillators , 2006, Theoretical Biology and Medical Modelling.

[47]  Rebecca L. Salbu,et al.  Jet lag: current and potential therapies. , 2011, P & T : a peer-reviewed journal for formulary management.

[48]  Haruhiko Soma,et al.  Transcriptional oscillation of canonical clock genes in mouse peripheral tissues , 2004, BMC Molecular Biology.

[49]  Denis Thieffry,et al.  Petri net modelling of biological regulatory networks , 2008, J. Discrete Algorithms.

[50]  L. Donehower,et al.  Disrupting Circadian Homeostasis of Sympathetic Signaling Promotes Tumor Development in Mice , 2010, PloS one.

[51]  Xiaoming Yang,et al.  Down regulation of circadian clock gene Period 2 accelerates breast cancer growth by altering its daily growth rhythm , 2009, Breast Cancer Research and Treatment.

[52]  J. Takahashi,et al.  Molecular components of the mammalian circadian clock. , 2006, Human molecular genetics.

[53]  Monika Heiner,et al.  Model Validation of Biological Pathways Using Petri Nets - Demonstrated for Apoptosis , 2003, CMSB.

[54]  René Thomas.  Regulatory networks seen as asynchronous automata: A logical description , 1991 .

[55]  Franck Delaunay,et al.  Effects of Chronic Jet Lag on Tumor Progression in Mice , 2004, Cancer Research.

[56]  Steven M. Reppert,et al.  Posttranslational Mechanisms Regulate the Mammalian Circadian Clock , 2001, Cell.

[57]  G. Wahl,et al.  c-Myc can induce DNA damage, increase reactive oxygen species, and mitigate p53 function: a mechanism for oncogene-induced genetic instability. , 2002, Molecular cell.

[58]  S. Yamaguchi,et al.  Control Mechanism of the Circadian Clock for Timing of Cell Division in Vivo , 2003, Science.

[59]  J. Takahashi,et al.  Central and peripheral circadian clocks in mammals. , 2012, Annual review of neuroscience.

[60]  René Thomas,et al.  Kinetic logic : a Boolean approach to the analysis of complex regulatory systems : proceedings of the EMBO course "Formal analysis of genetic regulation," held in Brussels, September 6-16, 1977 , 1979 .

[61]  Katsumi Inoue,et al.  Proceedings of the Twenty-Second International Joint Conference on Artificial Intelligence Logic Programming for Boolean Networks , 2022 .

[62]  Ueli Schibler,et al.  Liver Regeneration Clocks On , 2003, Science.

[63]  Alexander Greer,et al.  Chemistry. Enhanced: a view of unusual peroxides. , 2003, Science.

[64]  Peter Morfeld,et al.  Shift Work and Cancer: The Evidence and the Challenge , 2011 .

[65]  Ina Koch,et al.  Model validation of biological pathways using Petri nets , 2004 .

[66]  Jitender S. Deogun,et al.  Yeast pheromone pathway modeling using Petri nets , 2014, BMC Bioinformatics.

[67]  Gilles Bernot,et al.  Discrete Delay Model for the Mammalian Circadian Clock , 2007, Complexus.

[68]  A. Goldbeter,et al.  Modeling the mammalian circadian clock: sensitivity analysis and multiplicity of oscillatory mechanisms. , 2004, Journal of Theoretical Biology.

[69]  Adrien Richard,et al.  Formal Methods for Modeling Biological Regulatory Networks , 2006 .

[70]  F. Lévi,et al.  Cross-talks between circadian timing system and cell division cycle determine cancer biology and therapeutics. , 2007, Cold Spring Harbor symposia on quantitative biology.

[71]  Wolfgang Reisig,et al.  Carl Adam Petri and "Petri Nets" , 2007 .

[72]  Phyllis C Zee,et al.  Circadian Rhythm Abnormalities , 2013, Continuum.

[73]  Peng Huang,et al.  The Circadian Gene Period2 Plays an Important Role in Tumor Suppression and DNA Damage Response In Vivo , 2002, Cell.

[74]  K. Kadota,et al.  Genome-wide Expression Analysis of Mouse Liver Reveals CLOCK-regulated Circadian Output Genes* , 2003, Journal of Biological Chemistry.

[75]  K. Yu,et al.  Variants in circadian genes and prostate cancer risk: a population-based study in China , 2007, Prostate Cancer and Prostatic Diseases.

[76]  J. Hansen.  Risk of Breast Cancer After Night- and Shift Work: Current Evidence and Ongoing Studies in Denmark , 2006, Cancer Causes & Control.

[77]  K Kume,et al.  Interacting molecular loops in the mammalian circadian clock. , 2000, Science.

[78]  Francis Lévi,et al.  Circadian Disruption in Experimental Cancer Processes , 2009, Integrative cancer therapies.

[79]  N. Lightfoot,et al.  Rotating shift work and risk of prostate cancer. , 2007, Epidemiology.

[80]  H. Herzel,et al.  Modeling feedback loops of the Mammalian circadian oscillator. , 2004, Biophysical journal.

[81]  Aurélien Naldi,et al.  Logical modelling of gene regulatory networks with GINsim. , 2012, Methods in molecular biology.

[82]  Vincent Laudet,et al.  The days and nights of cancer cells. , 2003, Cancer research.

[83]  Andrea Sackmann,et al.  Petri net based model of the body iron homeostasis , 2007, J. Biomed. Informatics.

[84]  N. Le,et al.  Cohort study of Air Canada pilots: mortality, cancer incidence, and leukemia risk. , 1996, American journal of epidemiology.

[85]  Aurélien Naldi,et al.  Logical modelling of regulatory networks with GINsim 2.3 , 2009, Biosyst..

[86]  U. Niazi,et al.  Formal Modeling and Analysis of the MAL-Associated Biological Regulatory Network: Insight into Cerebral Malaria , 2012, PloS one.

[87]  F. Fleury-Olela,et al.  Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus. , 2000, Genes & development.

[88]  A. B. Reddy,et al.  Circadian clocks: neural and peripheral pacemakers that impact upon the cell division cycle. , 2005, Mutation research.

[89]  A theoretical approach to the mechanism of jet lag using multiple-oscillator models , 2015 .

[90]  Satchidananda Panda,et al.  Circadian rhythms from flies to human , 2002, Nature.

[91]  A. Auvinen,et al.  Cancer incidence among 10,211 airline pilots: a Nordic study. , 2003, Aviation, space, and environmental medicine.