DOCSLIB.ORG

The Circadian Clock and Hepatocellular Cancer

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Circadian Clock and Hepatocellular Cancer 956 Editorial Cancer prevention through better sleeping habits: the circadian clock and hepatocellular cancer Katarzyna Trebska-McGowan, Trevor W. Reichman Division of Transplantation, Department of Surgery, Virginia Commonwealth University, Richmond, VA, USA Correspondence to: Trevor W. Reichman MD, PhD. Division of Transplant Surgery, Department of Surgery, Virginia Commonwealth University, PO Box 980057, Richmond, VA 23298-0057, USA. Email: [email protected]. Comment on: Kettner NM, Voicu H, Finegold MJ, et al. Circadian Homeostasis of Liver Metabolism Suppresses Hepatocarcinogenesis. Cancer Cell 2016;30:909-24. Submitted May 11, 2017. Accepted for publication May 19, 2017. doi: 10.21037/tcr.2017.06.06 View this article at: http://dx.doi.org/10.21037/tcr.2017.06.06 The incidence of hepatocellular cancer (HCC) has been NAFLD or NASH before progressing to cirrhosis (2,3). steadily increasing in the United States for the last several A recent publication by Kettner and colleagues proposes decades, and currently HCC constitutes the fastest growing that dysregulation of the circadian clock, also termed cause of cancer deaths in the country. The majority of chronic jet lag, can independently lead to the development HCC occurs in the setting of chronic liver disease with of liver cancer in a stepwise process beginning with the viral infections [hepatitis B virus (HBV) or hepatitis C virus development of fatty liver disease then progressing through (HCV)] and alcohol-related liver disease being the most steatohepatitis, fibrosis, and eventually developing into common risk factors. Recently non-alcoholic fatty liver HCC (4). disease (NAFLD) and non-alcoholic steatohepatitis (NASH) The biological clock is not unique to mammals as it plays have been recognized as conditions predisposing to the a role in the homeostasis of all eukaryotes (5,6). It is the development of end stage liver disease and HCC (1). It is circadian clock, not outside environments that determines estimated that in the next 10 years, NASH will become the behavior patterns and oscillations in the physiology leading indication for liver transplantation in the Western of species from single cell organisms to mammals (7). world (1,2). In humans, the circadian rhythm is governed by the NAFLD is extremely common in the Western suprachiasmatic nucleus (SCN), which acts as the “central population, and according to some reports roughly 30% clock”, and coordinates circadian rhythmicity of multiple of population is affected by it to a certain degree. The organ systems. The most potent exogenous stimulus that development of steatosis is a component of a complex, influences circadian pattern is ambient light. Most, if not multifactorial process that not only involves the liver, all organs, have their own biological clocks, which act as but also effects a range of metabolic processes in all body self-sustained autonomous oscillators that are connected by systems including certain epigenetic processes and the positive and negative feedback loops to the SCN by means circadian rhythm (3). This process, commonly referred of neuroendocrine and autonomic nervous systems. Many to as the metabolic syndrome, usually manifests with the processes such as immune function, hormone production, initial development of insulin resistance and liver steatosis. secretions of the gastrointestinal tract, body temperature, Subsequent oxidative stress and chronic inflammation in the sleep/wake cycles, as well as gene and protein expression, liver lead to the development of hepatic steatosis, followed are regulated by a number of clock genes and proteins, by fibrosis, and finally cirrhosis. Although liver cirrhosis and the expression of these genes varies between different is a powerful driver for the development of HCC, it is peripheral tissues in the body (6). not uncommon for carcinoma to develop in the setting of The major players in the regulation of the circadian © Translational Cancer Research. All rights reserved. tcr.amegroups.com Transl Cancer Res 2017;6(Suppl 6):S953-S956 S954 Trebska-McGowan and Reichman. Circadian rhythm and HCC clock at the molecular level are the transcription factors upregulated in comparison to normal stomach tissue, and CLOCK (circadian locomotor output cycles kaput) and expression of CRY1 was positively correlated with more BMAL1 (brain and muscle aryl hydrocarbon receptor advanced tumor stage (11). Acute lymphocytic leukemia and nuclear translocator-like 1), the genes hPer1, -2, and -3 non-Hodgkin lymphoma are also characterized by circadian (human period), and Cry1 and -2 (cryptochrome) and their deregulation of the c-Myc protein resulting from hyper- respective protein products PER and CRY. CLOCK- methylation of the BMAL1 gene (12). Downregulation BMAL1 heterodimer controls circadian oscillations by of clock genes has also been reported in gynecological upregulating PER and CRY proteins, which in turns malignancies of endometrial (13) and ovarian (14) origin. through negative feedback loop repress activity of the Breast cancer is one of the best studied malignancies CLOCK-BMAL1 complex. PER and CRY are ultimately with respect to the role of circadian rhythm in the process degraded, allowing the process to proceed in a cyclical of tumorigenesis. Many have reported that the CLOCK fashion; a process that usually takes about 24 h. Products of gene has significantly higher expression in mutated breast several metabolic processes ongoing throughout a person’s cancer tissue in comparison to unaffected tissue. Moreover, body influence the levels of transcription factors and genes estrogen-negative tumors, which carry worse prognosis, regulating the biological clock, and may ultimately alter upregulate CLOCK gene in comparison to hormone circadian rhythm (5,6). positive tumors (15). A reverse relationship is also observed Early in evolution and currently in non-developed for PER genes, with decreased expression conferring regions of the world, humans are awake during the day higher risk of breast malignancy and worse prognosis (6). and are asleep at night. However, in modern industrialized Interestingly, there are several publications which focus societies, people’s circadian rhythm is often altered by mostly on nurses and airline crews that report increased artificially lit environments, shift work and transcontinental incidence of breast cancer among women working night travel. All these factors contribute to interruption of shifts, with relative risk of 1.2–1.8 (16-18). However, circadian hemostasis, which has been implicated in the these studies focused on nocturnal exposure to light and development of multiple diseases, ranging from sleep and decreased levels of melatonin as risk factors, not on the mood disorders to hypertension, the metabolic syndrome, molecular mechanism involved in circadian rhythmicity. and cancer (5-7). Cell cycle dysregulation is a cardinal That being said, the epidemiologic data demonstrating an feature of cancer cells and the cell cycle is strongly linked association between nightshift work and increased risk of to a person’s biological clock. Many common, oncogenic breast malignancy is intriguing and warrant more in depth transformations lead to downstream mutations of circadian studies. genes and proteins that in turn further contribute to There is a breadth of information derived from studies tumorigenesis by affecting tumor suppressors and proto- of HCC in animal that demonstrates a strong correlation oncogenes that naturally display circadian rhythmicity. between altered biological clock genes and malignant Multiple cell cycle regulatory genes have been associated transformation of the liver. Filipski et al. compared two with circadian clock including c-Myc, p53, cyclin D, and cohorts of mice exposed to known liver carcinogen RAS family (5,8,9). Circadian genes have been implicated diethylnitrosamine (DEN) with one group being raised in in multiple cancers including hematologic malignancies, normal 12-hour day-night conditions, and the other group squamous cell carcinoma of head and neck, breast and was submitted to chronic jet lag. The mice from the second gastrointestinal caners (5-9). Although the exact mechanism group were found to have an increase number and larger is not clearly understood, it is hypothesized that alterations liver tumors than the controls (19). In addition, several in circadian rhythm result in epigenetic modifications studies looking at HCC tumor samples have also shown and chromatin remodeling further contributing to a correlation between an altered biologic clock and the carcinogenesis (6,8). development of HCC (20-22). To our knowledge, there is Some known circadian genes, in particular PER, no published epidemiologic data that explores the incidence CRY and BMAL1 were found to be downregulated in of HCC in subjects working unusual hours, especially night patients with squamous cell carcinoma of head and neck. shifts. These alterations were associated with larger tumor size, In their recent project, Kettner et al., using a mouse deeper invasion, more advanced cancer stage and shorter model, showed that dysregulation of circadian genes and survival (10). In gastric cancer PER2 was more likely to be the biological clock leads to activation of several oncogenic © Translational Cancer Research. All rights reserved. tcr.amegroups.com Transl Cancer Res 2017;6(Suppl 6):S953-S956 Translational Cancer Research, Vol 6, Suppl 6 August 2017 S955 pathways (4). In normal, non-jet-lagged mice, cholestasis
Load more

Recommended publications
  • A Wheel of Time: the Circadian Clock, Nuclear Receptors, and Physiology
    Downloaded from genesdev.cshlp.org on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press PERSPECTIVE A wheel of time: the circadian clock, nuclear receptors, and physiology Xiaoyong Yang1 Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06519, USA It is a long-standing view that the circadian clock func- The rhythmic production and circulation of many tions to proactively align internal physiology with the hormones and metabolites within the endocrine system 24-h rotation of the earth. Recent studies, including one is instrumental in regulating regular physiological pro- by Schmutz and colleagues (pp. 345–357) in the February cesses such as reproduction, blood pressure, and metabo- 15, 2010, issue of Genes & Development, delineate strik- lism. Levels of circulating estrogen and progesterone ingly complex connections between molecular clocks and fluctuate with the menstrual cycle, which in turn affect nuclear receptor signaling pathways, implying the exis- circadian rhythms in women (Shechter and Boivin 2010). tence of a large-scale circadian regulatory network co- In parallel with a diurnal rhythm in circulating adrenocor- ordinating a diverse array of physiological processes to ticotropic hormone, secretion of glucocorticoids and aldo- maintain dynamic homeostasis. sterone from the adrenal gland rises before awakening (Weitzman 1976). Glucocorticoids boost energy produc- tion, and aldosterone increases blood pressure, together gearing up the body for the activity phase. Similarly, Light from the sun sustains life on earth. The 24-h plasma levels of thyroid-stimulating hormone and triiodo- rotation of the earth exposes a vast number of plants thyronine have a synchronous diurnal rhythm (Russell and animals to the light/dark cycle.
    [Show full text]
  • Melatonin Synthesis and Clock Gene Regulation in the Pineal Organ Of
    General and Comparative Endocrinology 279 (2019) 27–34 Contents lists available at ScienceDirect General and Comparative Endocrinology journal homepage: www.elsevier.com/locate/ygcen Review article Melatonin synthesis and clock gene regulation in the pineal organ of teleost fish compared to mammals: Similarities and differences T ⁎ Saurav Saha, Kshetrimayum Manisana Singh, Braj Bansh Prasad Gupta Environmental Endocrinology Laboratory, Department of Zoology, North-Eastern Hill University, Shillong 793022, India ARTICLE INFO ABSTRACT Keywords: The pineal organ of all vertebrates synthesizes and secretes melatonin in a rhythmic manner due to the circadian Aanat gene rhythm in the activity of arylalkylamine N-acetyltransferase (AANAT) – the rate-limiting enzyme in melatonin Circadian rhythm synthesis pathway. Nighttime increase in AANAT activity and melatonin synthesis depends on increased ex- Clock genes pression of aanat gene (a clock-controlled gene) and/or post-translation modification of AANAT protein. In Melatonin synthesis mammalian and avian species, only one aanat gene is expressed. However, three aanat genes (aanat1a, aanat1b, Pineal organ and aanat2) are reported in fish species. While aanat1a and aanat1b genes are expressed in the fish retina, the Photoperiod fi Temperature nervous system and other peripheral tissues, aanat2 gene is expressed exclusively in the sh pineal organ. Clock genes form molecular components of the clockwork, which regulates clock-controlled genes like aanat gene. All core clock genes (i.e., clock, bmal1, per1, per2, per3, cry1 and cry2) and aanat2 gene (a clock-controlled gene) are expressed in the pineal organ of several fish species. There is a large body of information on regulation of clock genes, aanat gene and melatonin synthesis in the mammalian pineal gland.
    [Show full text]
  • Role of the Nuclear Receptor Rev-Erb Alpha in Circadian Food Anticipation and Metabolism Julien Delezie
    Role of the nuclear receptor Rev-erb alpha in circadian food anticipation and metabolism Julien Delezie To cite this version: Julien Delezie. Role of the nuclear receptor Rev-erb alpha in circadian food anticipation and metabolism. Neurobiology. Université de Strasbourg, 2012. English. NNT : 2012STRAJ018. tel- 00801656 HAL Id: tel-00801656 https://tel.archives-ouvertes.fr/tel-00801656 Submitted on 10 Apr 2013 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. UNIVERSITÉ DE STRASBOURG ÉCOLE DOCTORALE DES SCIENCES DE LA VIE ET DE LA SANTE CNRS UPR 3212 · Institut des Neurosciences Cellulaires et Intégratives THÈSE présentée par : Julien DELEZIE soutenue le : 29 juin 2012 pour obtenir le grade de : Docteur de l’université de Strasbourg Discipline/ Spécialité : Neurosciences Rôle du récepteur nucléaire Rev-erbα dans les mécanismes d’anticipation des repas et le métabolisme THÈSE dirigée par : M CHALLET Etienne Directeur de recherche, université de Strasbourg RAPPORTEURS : M PFRIEGER Frank Directeur de recherche, université de Strasbourg M KALSBEEK Andries
    [Show full text]
  • Correlation Between Circadian Gene Variants and Serum Levels of Sex Steroids and Insulin-Like Growth Factor-I
    3268 Correlation between Circadian Gene Variants and Serum Levels of Sex Steroids and Insulin-like Growth Factor-I Lisa W. Chu,1,2 Yong Zhu,3 Kai Yu,1 Tongzhang Zheng,3 Anand P. Chokkalingam,4 Frank Z. Stanczyk,5 Yu-Tang Gao,6 and Ann W. Hsing1 1Division of Cancer Epidemiology and Genetics and 2Cancer Prevention Fellowship Program, Office of Preventive Oncology, National Cancer Institute, NIH, Bethesda, Maryland; 3Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut; 4Division of Epidemiology, School of Public Health, University of California at Berkeley, Berkeley, California; 5Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, California; and 6Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China Abstract A variety of biological processes, including steroid the GG genotype. In addition, the PER1 variant was hormone secretion, have circadian rhythms, which are associated with higher serum levels of sex hormone- P influenced by nine known circadian genes. Previously, binding globulin levels ( trend = 0.03), decreasing we reported that certain variants in circadian genes 5A-androstane-3A,17B-diol glucuronide levels P P were associated with risk for prostate cancer. To pro- ( trend = 0.02), and decreasing IGFBP3 levels ( trend = vide some biological insight into these findings, we 0.05). Furthermore, the CSNK1E variant C allele was examined the relationship of five variants of circadian associated with higher
    [Show full text]
  • Effects of Circadian Clock Genes and Health-Related
    RESEARCH ARTICLE Effects of circadian clock genes and health- related behavior on metabolic syndrome in a Taiwanese population: Evidence from association and interaction analysis Eugene Lin1,2,3*, Po-Hsiu Kuo4, Yu-Li Liu5, Albert C. Yang6,7, Chung-Feng Kao8, Shih- Jen Tsai6,7* 1 Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, 2 Vita Genomics, Inc., Taipei, Taiwan, 3 TickleFish Systems Corporation, Seattle, Western Australia, United States of America, a1111111111 4 Department of Public Health, Institute of Epidemiology and Preventive Medicine, National Taiwan a1111111111 University, Taipei, Taiwan, 5 Center for Neuropsychiatric Research, National Health Research Institutes, a1111111111 Miaoli County, Taiwan, 6 Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan, 7 Division of Psychiatry, National Yang-Ming University, Taipei, Taiwan, 8 Department of Agronomy, College a1111111111 of Agriculture & Natural Resources, National Chung Hsing University, Taichung, Taiwan a1111111111 * [email protected] (EL); [email protected] (SJT) Abstract OPEN ACCESS Citation: Lin E, Kuo P-H, Liu Y-L, Yang AC, Kao C- Increased risk of developing metabolic syndrome (MetS) has been associated with the cir- F, Tsai S-J (2017) Effects of circadian clock genes cadian clock genes. In this study, we assessed whether 29 circadian clock-related genes and health-related behavior on metabolic (including ADCYAP1, ARNTL, ARNTL2, BHLHE40, CLOCK, CRY1, CRY2, CSNK1D, syndrome in a Taiwanese population: Evidence from association and interaction analysis. PLoS CSNK1E, GSK3B, HCRTR2, KLF10, NFIL3, NPAS2, NR1D1, NR1D2, PER1, PER2, ONE 12(3): e0173861. https://doi.org/10.1371/ PER3, REV1, RORA, RORB, RORC, SENP3, SERPINE1, TIMELESS, TIPIN, VIP, and journal.pone.0173861 VIPR2) are associated with MetS and its individual components independently and/or Editor: Etienne Challet, CNRS, University of through complex interactions in a Taiwanese population.
    [Show full text]
  • Retinoic Acid-Related Orphan Receptor Rorβ, Circadian Rhythm Abnormalities and Tumorigenesis (Review)
    INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 35: 1493-1500, 2015 Retinoic acid-related orphan receptor RORβ, circadian rhythm abnormalities and tumorigenesis (Review) SHUJIONG FENG1, SONG XU1, ZHENZHEN WEN1 and YONGLIANG ZHU1,2 1Laboratory of Gastroenterology, The Second Affiliated Hospital of Zhejiang University, School of Medicine; 2Cancer Institute and Education Ministry Key Laboratory of Cancer Prevention and Intervention, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China Received August 8, 2014; Accepted March 12, 2015 DOI: 10.3892/ijmm.2015.2155 Abstract. Nuclear receptors are a superfamily of transcription and have important physiological functions in cell develop- factors including the steroid hormone receptors, non-steroid ment and differentiation, circadian rhythm, metabolism and hormone receptors and the orphan nuclear receptor family. immune regulation. NRs consist of three components: the Retinoic acid-related orphan receptor (ROR)β, as a member of steroid hormone receptors, non-steroid hormone receptors the orphan nuclear receptor family, plays an important regula- and the orphan nuclear receptor family. Steroid and non- tory role in the maintenance of a variety of physiological and steroid hormone receptors have specific ligands, including pathological processes. RORβ has been determined to act as steroid hormones, thyroid hormones, retinoic acids and fatty an osteogenic repressor in regulating bone formation, and is acids. Ligands for orphan NRs have not yet been determined. involved in regulating circadian rhythm. The findings of recent Retinoic acid-related orphan receptors (RORs), also known studies concerning the association between tumorigenesis as nuclear receptor subfamily 1 group F members (NR1F), and circadian rhythm have shown that an aberrant circadian are specified by gene sequences, which are homologous to rhythm may promote tumorigenesis and tumor progression.
    [Show full text]
  • Analysis of Gene Expression in Wild Type and Notch1 Mutant Retinal Cells by Single Cell Profiling Karolina Mizeracka1, Jeffrey M
    Research Article Developmental Dynamics DOI 10.1002/dvdy.24006 Analysis of gene expression in wild type and Notch1 mutant retinal cells by single cell profiling Karolina Mizeracka1, Jeffrey M. Trimarchi1,2, Michael B. Stadler3, Constance L. Cepko1,4 1 Department of Genetics, Department of Ophthalmology, Harvard Medical School, Boston, MA 02115 2 Current Address: Department of Genetics, Development and Cell Biology, Iowa State University, Ames, IA 50014 3 Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland 4 Howard Hughes Medical Institute, Department of Genetics, Department of Ophthalmology, Harvard Medical School, Boston, MA 02115 Correspondence: Constance Cepko 77 Avenue Louis Pasteur, Boston, MA 02115 Phone: (617) 432-7618 Fax: (617) 432-7595 Running title: Single cell profiling of Notch1 mutant retinal cells Key words: retina, progenitor, microarray, cell fate Summary: • Profiling of individual Notch1 deficient and wild type postnatal retinal cells on microarrays reveals changes in gene expression obscured by whole tissue analysis • Notch1 deficient cells downregulate progenitor and cell cycle markers with a concomitant upregulation in early rod photoreceptor markers • Based on classification, single Notch1 deficient and wild type cells represent Developmental Dynamics transition from progenitor to postmitotic cell • Individual wild type retinal cells express cell type markers of both photoreceptors and interneurons Grant sponsor and number: National Institutes of Health Grant R01EY09676 Accepted Articles are accepted, unedited articles for future issues, temporarily published online in advance of the final edited version. © 2013 Wiley Periodicals, Inc. Received: Mar 04, 2013; Revised: May 02, 2013; Accepted: May 13, 2013 Developmental Dynamics Page 2 of 66 Abstract Background: The vertebrate retina comprises sensory neurons, the photoreceptors, as well as many other types of neurons and one type of glial cell.
    [Show full text]
  • CRY1 and NPAS2 Are Associated with Unipolar Major Depression and CLOCK and VIP with Bipolar Disorder
    Neuropsychopharmacology (2010) 35, 1279–1289 & 2010 Nature Publishing Group All rights reserved 0893-133X/10 $32.00 www.neuropsychopharmacology.org Differential Association of Circadian Genes with Mood Disorders: CRY1 and NPAS2 are Associated with Unipolar Major Depression and CLOCK and VIP with Bipolar Disorder 1 ` 1 2 3 4 Virginia Soria ,Erika Martı´nez-Amoro´s , Geo`rgia Escaramı´s , Joaquı´n Valero , Rosario Pe´rez-Egea , 5 3 4 5 1,6 Cecilia Garcı´a , Alfonso Gutie´rrez-Zotes , Dolors Puigdemont ,Mo`nica Baye´s , Jose´ M Crespo , 3 3 3 1,6 4 1,6 Lourdes Martorell , Elisabet Vilella , Antonio Labad , Julio Vallejo ,Vı´ctor Pe´rez , Jose´ M Mencho´n , 2,7 ,2 1,6 Xavier Estivill ,Mo`nica Grataco`s* and Mikel Urretavizcaya 1 CIBERSAM (CIBER en Salud Mental), Mood Disorders Clinical and Research Unit, Psychiatry Department, Bellvitge University Hospital, 2 Barcelona, Spain; CIBERESP (CIBER en Epidemiologı´a y Salud Pu´blica), Genes and Disease Program, Center for Genomic Regulation (CRG), Barcelona, Spain; 3Hospital Psiquiatric Universitari Institut Pere Mata, IISPV, Universitat Rovira i Virgili, Reus, Spain; 4CIBERSAM (CIBER en Salud Mental), Psychiatry Department, Hospital de la Santa Creu i Sant Pau, Universitat Auto`noma de Barcelona, Barcelona, Spain; 5Genomics 6 Core Facility and Centro Nacional de Genotipado (CeGen), Center for Genomic Regulation (CRG), Barcelona, Spain; Department of Clinical 7 Sciences, Bellvitge Campus, Barcelona University, Barcelona, Spain; Experimental and Health Sciences Department, Pompeu Fabra University, Barcelona, Spain Disruptions in circadian rhythms have been described in mood disorders (MD), but the involvement of genetic variation in genes pertaining to the molecular circadian machinery in the susceptibility to MD has not been conclusively determined.
    [Show full text]
  • Crosstalk Between Xenobiotics Metabolism and Circadian Clock
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector FEBS Letters 581 (2007) 3626–3633 Minireview Crosstalk between xenobiotics metabolism and circadian clock Thierry Claudela, Gaspard Cretenetb,c, Anne Saumetb,c, Fre´de´ric Gachonb,c,* a Department of Pediatrics, Research Laboratory, University Medical Center Groningen, Groningen, ND-9700 RB, The Netherlands b Inserm, Equipe Avenir, Montpellier F-34396, France c CNRS, Institut de Ge´ne´tique Humaine, UPR 1142, Montpellier F-34396, France Received 22 February 2007; revised 30 March 2007; accepted 3 April 2007 Available online 17 April 2007 Edited by Robert Barouki metabolism and detoxification are regulated in an anticipatory Abstract Many aspects of physiology and behavior in organ- isms from bacteria to man are subjected to circadian regulation. fashion by the circadian clock [2]. For example, rest and activ- Indeed, the major function of the circadian clock consists in the ity cycles, heart rate, blood pressure, bile and urine produc- adaptation of physiology to daily environmental change and the tion, drug metabolism and transport in liver and intestine as accompanying stresses such as exposition to UV-light and food- well as endocrine functions are all subjected to daily fluctua- contained toxic compounds. In this way, most aspects of xenobi- tions. The mammalian timing system is organized in a hierar- otic detoxification are subjected to circadian regulation. These chical manner with a central pacemaker located in the phenomena are now considered as the molecular basis for the suprachiasmatic nucleus (SCN) of the hypothalamus which time-dependence of drug toxicities and efficacy.
    [Show full text]
  • Expression of Circadian Genes Correlates with Liver Metastasis and Outcomes in Colorectal Cancer
    ONCOLOGY REPORTS 25: 1439-1446, 2011 Expression of circadian genes correlates with liver metastasis and outcomes in colorectal cancer TakaSHI OSHIMA1, SEIICH TakENOSHITA2, MAKOTO AKAIKE3, CHIKARA KUNISAKI1, SHOICH FUJII1, AKITO NOZAKI1, KAZUSHI NUMATA1, MANABU SHIOZawa3, YaSUSHI RINO4, KATSUAKI TaNAKA1, MUNETAKA MASUDA4 and TOSHIO IMADA4 1Gastroenterological Center, Yokohama City University Medical Center 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024; 2Department of Surgery, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1247; 3Department of Surgery, Kanagawa Cancer Center, 1-1-2 Nakao, Asahi-ku, Yokohama, Kanagawa 241-0815; 4Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan Received December 14, 2010; Accepted February 7, 2011 DOI: 10.3892/or.2011.1207 Abstract. Circadian rhythms are daily oscillations in various the Per1 gene may thus be useful predictors of liver metastasis. biological processes, generated by the feedback loops of eight Moreover, reduced expression of the Per2 gene may be a core circadian genes: Period1 (Per1), Period2 (Per2), Period3 predictor of outcomes in patients with colorectal cancer. (Per3), Cryptochrome1 (Cry1), Cryptochrome2 (Cry2), Clock, Bmal1 and Casein Kinase I ε (CKIε). Recent studies have Introduction suggested that circadian genes participate in the growth and development of various cancers. This study examined the rela- Circadian rhythms are daily oscillations in various biologic tions of circadian gene expression to clinicopathological factors processes. In mammals, the master circadian pacemaker and outcomes in patients with colorectal cancer. We studied is located in the suprachiasmatic nuclei (SCN) (1). The surgical specimens of cancer tissue and adjacent normal master circadian clock coordinates peripheral circadian mucosa obtained from 202 patients with untreated colorectal clocks within virtually every cell in the body (2).
    [Show full text]
  • Type of the Paper (Article
    The Consumption of Cholesterol-Enriched Diets Conditions the Development of a Subtype of HCC with High Aggressiveness and Poor Prognosis Arturo Simoni-Nieves, Soraya Salas-Silva, Lisette Chávez-Rodríguez, Alejandro Escobedo-Calvario, Matthis Desoteux, Leticia Bucio, Verónica Souza, Roxana U. Miranda-Labra, Linda E. Muñoz-Espinosa, Cédric Coulouarn, María Concepción Gutiérrez-Ruiz, Jens U. Marquardt and Luis E. Gomez-Quiroz Figure S1. A) Gross inspection of mice fed with the different diets and treated or not with DEN. Representative image of at least eight animals, white arrows show adipose tissue. B) Tumor gross inspection of mice under different diets. Repre- sentative image of at least eight livers, yellow arrows show vascularity. Images are representative of at least eight mice. Cancers 2021, 13, 1721. https://doi.org/10.3390/cancers13071721 www.mdpi.com/journal/cancers Cancers 2021, 13, 1721 2 of 29 Figure S2. Expression of eight randomly selected genes in samples not included in the RNA-seq, as technical and biological validation. Each graph plots the individual data points, the superimpose horizontal line indicates the arithmetic mean and error bars showing ± SEM. ** p < 0.01 vs CW group; & p < 0.05 vs diet control. Cancers 2021, 13, 1721 3 of 29 Figure S3. Expression of the 4 genes differentially overexpressed related to high lipid overload with potential relevance in tumor promotion: Mthfd1, Slc41a3, Fabp5, Igdcc4. Each graph plots the individual data points, the superimpose hori- zontal line indicates the arithmetic mean and error bars showing ± SEM. ** p < 0.01 vs CW group. Table S1. Mice groups under different diets and treatments.
    [Show full text]
  • Up-Regulation of PER3 Expression Is Correlated with Better Clinical Outcome in Acute Leukemia
    ANTICANCER RESEARCH 35: 6615-6622 (2015) Up-regulation of PER3 Expression Is Correlated with Better Clinical Outcome in Acute Leukemia MING-YU YANG1, PAI-MEI LIN2, HUI-HUA HSIAO3,4, JUI-FENG HSU5, HUGO YOU-HSIEN LIN5,6, CHENG-MING HSU1,7, I-YA CHEN1, SHENG-WEN SU1, YI-CHANG LIU3,4 and SHENG-FUNG LIN3,4 1Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan, R.O.C.; 2Department of Nursing, I-Shou University, Kaohsiung City, Taiwan, R.O.C.; 3Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung City, Taiwan, R.O.C.; 4Faculty of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan, R.O.C.; 5Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan, R.O.C.; 6Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan, R.O.C.; 7Department of Otolaryngology, Kaoshiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, R.O.C. Abstract. Background: Altered expression of circadian treatment. Conclusion: Circadian clock genes are altered in clock genes has been linked to various types of cancer. This patients with acute leukemia and up-regulation of PER3 is study aimed to investigate whether these genes are also correlated with a better clinical outcome. altered in acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). Materials and Methods: The expression Acute leukemia comprises about 20,000 cancer diagnoses profiles of nine circadian clock genes of peripheral blood and 10,000 deaths in the United States each year (1).
    [Show full text]