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Epigenetic modifications in colorectal cancer
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Guo, Yue. Epigenetic modifications in colorectal cancer. Retrieved from https://doi.org/doi:10.7282/T35T3PKZ

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TitleEpigenetic modifications in colorectal cancer
NameGuo, Yue (author); Kong, Ah-Ng Tony (chair); Suh, Nanjoo (internal member); Andoulakis, Ioannis (internal member); Cai, Li (outside member); Rutgers University; School of Graduate Studies
Date Created2017
Other Date2017-10 (degree)
SubjectPharmaceutical Science, Colon (Anatomy)--Cancer--Prevention
Extent1 online resource (xvii, 234 p. : ill.)
DescriptionColorectal cancer is the third most common cancer worldwide and remains the leading cause of cancer-related death in the world. Emerging evidence has suggested that epigenetic mechanisms play an important role in colorectal carcinogenesis. It is now recognized that the interplay of DNA methylation, post-translational histone modification, and non-coding RNAs can interact with genetic defects to drive tumorigenesis. The early onset, reversibility, and dynamic nature of such epigenetic modifications enable them to be developed as promising cancer biomarkers and preventive targets. Aspirin and curcumin are widely investigated chemopreventive candidates for colorectal cancer. However, the precise mechanisms of their action have not been fully understood. Therefore, this dissertation research aimed to identify novel epigenetic alterations in colorectal carcinogenesis and to elucidate the mechanisms of colorectal cancer prevention by aspirin and curcumin in epigenetic perspective. Genome-wide DNA methylation profiles indicated that adenomatous polyps from Apc min/+ mice exhibited extensive aberrant DNA methylation that affected certain signaling pathways. Using human colorectal cancer cell lines, we demonstrated that inhibitory effect of curcumin on anchorage-independent growth of HT29 cells involves, at least in part, the epigenetic demethylation and up-regulation of tumor suppressor gene DLEC1. Chronic inflammation appears to enhance the risk of colorectal cancer. Using an azoxymethane-initiated and dextran sulfate sodium-promoted inflammation associated colon cancer animal model, we demonstrated the chemopreventive effect of aspirin. Our results identified a novel epigenetic mechanism of aspirin in attenuating inflammation in colon cancer via the inhibition of histone deacetylases and the modification of H3K27ac marks that suppress iNos, Tnf-α, and iL6. By using the similar animal model, we provided the first evidence in support of the chemopreventive effect of a combination of low-dose aspirin and curcumin in colitis-accelerated colorectal cancer. The transcriptional profile obtained from RNA-seq in our study provides a framework for identifying the mechanisms under carcinogenesis process from normal colonic tissue to tumor development as well as the cancer inhibitory effects and potential molecular targets of aspirin and curcumin.
NotePh.D.
NoteIncludes bibliographical references
Noteby Yue Guo
Genretheses, ETD doctoral
Persistent URLhttps://doi.org/doi:10.7282/T35T3PKZ
Languageeng
CollectionSchool of Graduate Studies Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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