Aberrant DNA methylation of miR‐219 promoter in long‐term night shiftworkers

The idea that shiftwork may be carcinogenic in humans has gained widespread attention since the pioneering work linking shiftwork to breast cancer over two decades ago. However, the biomolecular consequences of long‐term shiftwork exposure have not been fully explored. In this study, we performed a genome‐wide CpG island methylation assay of microRNA (miRNA) promoters in long‐term night shiftworkers and day workers. This analysis indicated that 50 CpG loci corresponding to 31 miRNAs were differentially methylated in night shiftworkers compared to day workers, including the circadian‐relevant miR‐219, the expression of which has been implicated in several cancers. A genome‐wide expression microarray assay was carried out in a miR‐219‐overexpressed MCF‐7 breast cancer cell line, which identified 319 differentially expressed transcripts. The identified transcriptional targets were analyzed for network and functional interrelatedness using the Ingenuity Pathway Analysis (IPA) software. Overexpression of miR‐219 in MCF‐7 breast cancer cells resulted in accentuated expression of apoptosis‐ and proliferation‐related anti‐viral immunodulators of the Jak‐STAT and NF‐κβ pathways. These findings suggest that long‐term night shiftwork exposure may lead to the methylation‐dependent downregulation of miR‐219, which may in turn lead to the downregulation of immunomediated antitumor activity and increased breast cancer risk. Environ. Mol. Mutagen. 54:406–413, 2013. © 2013 Wiley Periodicals, Inc.

[1]  R. Singaravelu,et al.  Oncolytic Viruses , 2021, Nature.

[2]  U. Vogel,et al.  Methylation alterations at imprinted genes detected among long‐term shiftworkers , 2013, Environmental and molecular mutagenesis.

[3]  R. Stevens,et al.  Genetic and epigenetic associations of circadian gene TIMELESS and breast cancer risk , 2012, Molecular carcinogenesis.

[4]  Ruiqi Wang,et al.  MicroRNA-mediated regulation in the mammalian circadian rhythm. , 2012, Journal of theoretical biology.

[5]  R. Stevens,et al.  Case-control study of shift-work and breast cancer risk in Danish nurses: impact of shift systems. , 2012, European journal of cancer.

[6]  J. Lee,et al.  NF-κB Directly Regulates Fas Transcription to Modulate Fas-mediated Apoptosis and Tumor Suppression* , 2012, The Journal of Biological Chemistry.

[7]  A. Neugut,et al.  DNA methylation in peripheral blood measured by LUMA is associated with breast cancer in a population‐based study , 2012, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[8]  A. Sehgal,et al.  Regulation of Circadian Behavioral Output via a MicroRNA-JAK/STAT Circuit , 2012, Cell.

[9]  G. Calin,et al.  Epigenetic regulation of microRNAs in cancer: an integrated review of literature. , 2011, Mutation research.

[10]  U. Vogel,et al.  Epigenetic Impact of Long-Term Shiftwork: Pilot Evidence From Circadian Genes and Whole-Genome Methylation Analysis , 2011, Chronobiology international.

[11]  P. Nicholson.  Shift work and chronic disease: the epidemiological evidence. , 2011, Occupational medicine.

[12]  V. Reed.  Shift Work, Light at Night, and the Risk of Breast Cancer , 2011 .

[13]  C. Harris,et al.  Genetic variation in microRNA networks: the implications for cancer research , 2010, Nature Reviews Cancer.

[14]  Shinji Tanaka,et al.  miR-124 and miR-203 are epigenetically silenced tumor-suppressive microRNAs in hepatocellular carcinoma. , 2010, Carcinogenesis.

[15]  W. Delprado,et al.  Mouse mammary tumor virus-like sequences in human breast cancer. , 2010, Cancer research.

[16]  T. Holford,et al.  The Core Circadian Gene Cryptochrome 2 Influences Breast Cancer Risk, Possibly by Mediating Hormone Signaling , 2010, Cancer Prevention Research.

[17]  T. Holford,et al.  CLOCK in breast tumorigenesis: genetic, epigenetic, and transcriptional profiling analyses. , 2010, Cancer research.

[18]  Sebastian Kadener,et al.  A role for microRNAs in the Drosophila circadian clock. , 2009, Genes & development.

[19]  J. Issa,et al.  Variable DNA methylation patterns associated with progression of disease in hepatocellular carcinomas. , 2008, Carcinogenesis.

[20]  H. Brenner,et al.  Epigenotyping in Peripheral Blood Cell DNA and Breast Cancer Risk: A Proof of Principle Study , 2008, PloS one.

[21]  B. Iacopetta,et al.  Mouse mammary tumor virus‐like env sequences in human breast cancer , 2008, International journal of cancer.

[22]  William Ignace Wei,et al.  Mature miR-184 as Potential Oncogenic microRNA of Squamous Cell Carcinoma of Tongue , 2008, Clinical Cancer Research.

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

[24]  R. Tamez-Guerra,et al.  Mouse Mammary Tumor Virus-Like Gene Sequences in Breast Cancer Samples of Mexican Women , 2007, Intervirology.

[25]  A. Tjønneland,et al.  Study design, exposure variables, and socioeconomic determinants of participation in Diet, Cancer and Health: A population-based prospective cohort study of 57,053 men and women in Denmark , 2007, Scandinavian journal of public health.

[26]  Takanobu Nakazawa,et al.  microRNA Modulation of Circadian-Clock Period and Entrainment , 2007, Neuron.

[27]  R. Stephens,et al.  Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. , 2006, Cancer cell.

[28]  John D. Storey,et al.  A network-based analysis of systemic inflammation in humans , 2005, Nature.

[29]  C. Croce,et al.  miRNAs, Cancer, and Stem Cell Division , 2005, Cell.

[30]  Young-In Kim.  Folate and DNA methylation: a mechanistic link between folate deficiency and colorectal cancer? , 2004, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[31]  A. Feinberg,et al.  Loss of IGF2 Imprinting: A Potential Marker of Colorectal Cancer Risk , 2003, Science.

[32]  J. Kirkwood,et al.  Interferon-alpha in tumor immunity and immunotherapy. , 2002, Cytokine & growth factor reviews.

[33]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.

[34]  B. Williams,et al.  Functional classification of interferon‐stimulated genes identified using microarrays , 2001, Journal of leukocyte biology.

[35]  R. Silverman,et al.  Caspase-dependent apoptosis by 2',5'-oligoadenylate activation of RNase L is enhanced by IFN-beta. , 2000, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[36]  S. Fawell,et al.  Interferon-beta gene therapy inhibits tumor formation and causes regression of established tumors in immune-deficient mice. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[37]  M. Vigneron,et al.  Constitutive expression of (2′–5′) oligo A synthetase confers resistance to picornavirus infection , 1987, Nature.

[38]  P. Laird,et al.  Genome-scale analysis of aberrant DNA methylation in colorectal cancer. , 2012, Genome Research.

[39]  V. Reed.  Shift work, light at night, and the risk of breast cancer. , 2011, AAOHN journal : official journal of the American Association of Occupational Health Nurses.

[40]  Shift work, light at night, and the risk of breast cancer: a guide to administrative action for health care institutions. , 2011, AAOHN journal : official journal of the American Association of Occupational Health Nurses.

[41]  Kemp H. Kernstine,et al.  DNA methylation biomarkers for lung cancer , 2011, Tumor Biology.

[42]  N. Rothman,et al.  Original Contribution Night-Shift Work and Breast Cancer Risk in a Cohort of Chinese Women , 2010 .

[43]  M. Boniotto,et al.  Modulation of the human cytokine response by interferon lambda-1 (IFN-λ1/IL-29) , 2007, Genes and Immunity.

[44]  M. Boniotto,et al.  Modulation of the human cytokine response by interferon lambda-1 (IFN-lambda1/IL-29). , 2007, Genes and immunity.