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RvD1 inhibits TNFα-induced c-Myc expression in normal intestinal epithelial cells and destabilizes hyper-expressed c-Myc in colon cancer cells

Cited 14 time in Web of Science Cited 14 time in Scopus
Authors
Zhong, Xiancai; Lee, Ha-Na; Surh, Young-Joon
Issue Date
2018-02
Citation
Biochemical and Biophysical Research Communications, Vol.496 No.2, pp.316-323
Keywords
Resolvin D1Colitis-associated cancerc-MycResolution of inflammationColon cancer
Abstract
Inflammatory bowel diseases, including ulcerative colitis and Crohn's disease, are persistent disorders that lead to development of colitis-associated cancer (CAC). Facilitated resolution of colitis has been addressed as a novel therapeutic strategy to control development of CAC. Resolvin D1 (RvD1) is an endogenous lipid mediator that is generated from docosahexaenoic acid during the resolution of inflammation. Although the pro-resolving effects of RvDs have been extensively investigated and well defined, the role for RvD1 in CAC remains largely unknown. In this study, we found that RvD1 inhibited the expression of c-Myc in normal colon cells stimulated with tumor necrosis factor-alpha (TNF alpha) and also in colon cancer cells. The suppression of TNF alpha-induced upregulation of c-Myc in normal cells was mediated through attenuation of NF-kappa B signaling. Notably, RvD1 destabilized the constitutively overexpressed cMyc protein in HCT 116 human colon cancer cells by stimulating its ubiquitination and subsequent proteasomal degradation. Further, we revealed that RvD1 stimulated c-Myc degradation through direct interaction with the AIX/FPR2 receptor. This interaction resulted in inhibition of activation of extracellular signal regulated kinase, thereby attenuating phosphorylation-dependent stabilization of c-Myc. (C) 2018 Elsevier Inc. All rights reserved.
ISSN
0006-291X
URI
https://hdl.handle.net/10371/172604
DOI
https://doi.org/10.1016/j.bbrc.2017.12.171
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Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
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