Multi-Omics Characterization of Inflammatory Bowel Disease-Induced Hyperplasia/Dysplasia in the Rag2-/-/Il10-/- Mouse Model.

作者: Qiyuan Han , Thomas J. Y. Kono , Charles G. Knutson , Nicola M. Parry , Christopher L. Seiler

DOI: 10.3390/IJMS22010364

关键词: Cancer researchEpigeneticsDNA methylationReduced representation bisulfite sequencingCarcinogenesisHelicobacter hepaticusBiologyTranscriptomeCancerDifferentially methylated regions

摘要: Epigenetic dysregulation is hypothesized to play a role in the observed association between inflammatory bowel disease (IBD) and colon tumor development. In present work, DNA methylome, hydroxymethylome, transcriptome analyses were conducted proximal tissues harvested from Helicobacter hepaticus (H. hepaticus)-infected murine model of IBD. Reduced representation bisulfite sequencing (RRBS) oxidative RRBS (oxRRBS) identified 1606 differentially methylated regions (DMR) 3011 hydroxymethylated (DhMR). These DMR/DhMR overlapped with genes that are associated gastrointestinal disease, cancer. RNA-seq revealed pronounced expression changes number inflammation Several including Duox2, Tgm2, Cdhr5, Hk2 exhibited both methylation/hydroxymethylation gene levels. Overall, our results suggest chronic triggers methylation hydroxymethylation patterns genome, altering key tumorigenesis potentially contributing initiation colorectal

参考文章(103)
Muthu K. Shanmugam, Gautam Sethi, Role of Epigenetics in Inflammation-Associated Diseases Subcellular Biochemistry. ,vol. 61, pp. 627- 657 ,(2013) , 10.1007/978-94-007-4525-4_27
Steven P. Lund, Dan Nettleton, Davis J. McCarthy, Gordon K. Smyth, Detecting Differential Expression in RNA-sequence Data Using Quasi-likelihood with Shrunken Dispersion Estimates Statistical Applications in Genetics and Molecular Biology. ,vol. 11, pp. 8- ,(2012) , 10.1515/1544-6115.1826
Michael C. Haffner, Alcides Chaux, Alan K. Meeker, David M. Esopi, Jonathan Gerber, Laxmi G. Pellakuru, Antoun Toubaji, Pedram Argani, Christine Iacobuzio-Donahue, William G. Nelson, George J. Netto, Angelo M. De Marzo, Srinivasan Yegnasubramanian, Global 5-hydroxymethylcytosine content is significantly reduced in tissue stem/progenitor cell compartments and in human cancers Oncotarget. ,vol. 2, pp. 627- 637 ,(2011) , 10.18632/ONCOTARGET.316
Masaki Okano, Shaoping Xie, En Li, Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases Nature Genetics. ,vol. 19, pp. 219- 220 ,(1998) , 10.1038/890
Matjaz Rokavec, Meryem Gülfem Öner, Heiko Hermeking, lnflammation-induced epigenetic switches in cancer. Cellular and Molecular Life Sciences. ,vol. 73, pp. 23- 39 ,(2016) , 10.1007/S00018-015-2045-5
J G Fox, F E Dewhirst, J G Tully, B J Paster, L Yan, N S Taylor, M J Collins, P L Gorelick, J M Ward, Helicobacter hepaticus sp. nov., a microaerophilic bacterium isolated from livers and intestinal mucosal scrapings from mice. Journal of Clinical Microbiology. ,vol. 32, pp. 1238- 1245 ,(1994) , 10.1128/JCM.32.5.1238-1245.1994
Marta Kulis, Manel Esteller, DNA methylation and cancer. Advances in Genetics. ,vol. 70, pp. 27- 56 ,(2010) , 10.1016/B978-0-12-380866-0.60002-2
Sigurdís Haraldsdóttir, Hulda M. Einarsdóttir, Agnes Smáradóttir, Aðalsteinn Gunnlaugsson, Þorvarður R. Hálfdánarson, , Krabbamein í ristli og endaþarmi - yfirlitsgrein Laeknabladid. ,vol. 100, pp. 75- 82 ,(2014) , 10.17992/LBL.2014.02.531
Ho-Chou Tu, Sarah Schwitalla, Zhirong Qian, Grace S. LaPier, Alena Yermalovich, Yuan-Chieh Ku, Shann-Ching Chen, Srinivas R. Viswanathan, Hao Zhu, Reiko Nishihara, Kentaro Inamura, Sun A. Kim, Teppei Morikawa, Kosuke Mima, Yasutaka Sukawa, Juhong Yang, Gavin Meredith, Charles S. Fuchs, Shuji Ogino, George Q. Daley, LIN28 cooperates with WNT signaling to drive invasive intestinal and colorectal adenocarcinoma in mice and humans Genes & Development. ,vol. 29, pp. 1074- 1086 ,(2015) , 10.1101/GAD.256693.114
Anne-France Le Rolle, Samuel J. Klempner, Christopher R. Garrett, Tara Seery, Eric M. Sanford, Sohail Balasubramanian, Jeffrey S. Ross, Philip J. Stephens, Vincent A. Miller, Siraj M. Ali, Vi K. Chiu, Identification and characterization of RET fusions in advanced colorectal cancer. Oncotarget. ,vol. 6, pp. 28929- 28937 ,(2015) , 10.18632/ONCOTARGET.4325