title: MicroRNA-26a/-26b-COX-2-MIP-2 Loop Regulates Allergic Inflammation and Allergic Inflammation-promoted Enhanced Tumorigenic and Metastatic Potential of Cancer Cells.
abstract: Cyclooxgenase-2 (COX-2) knock-out mouse experiments showed that COX-2 was necessary for in vivo allergic inflammation, such as passive cutaneous anaphylaxis, passive systemic anaphylaxis, and triphasic cutaneous allergic reaction. TargetScan analysis predicted COX-2 as a target of miR-26a and miR-26b. miR-26a/-26b decreased luciferase activity associated with COX-2-3'-UTR. miR-26a/-26b exerted negative effects on the features of in vitro and in vivo allergic inflammation by targeting COX-2. ChIP assays showed the binding of HDAC3 and SNAIL, but not COX-2, to the promoter sequences of miR-26a and miR-26b. Cytokine array analysis showed that the induction of chemokines, such as MIP-2, in the mouse passive systemic anaphylaxis model occurred in a COX-2-dependent manner. ChIP assays showed the binding of HDAC3 and COX-2 to the promoter sequences of MIP-2. In vitro and in vivo allergic inflammation was accompanied by the increased expression of MIP-2. miR-26a/-26b negatively regulated the expression of MIP-2. Allergic inflammation enhanced the tumorigenic and metastatic potential of cancer cells and induced positive feedback involving cancer cells and stromal cells, such as mast cells, macrophages, and endothelial cells. miR-26a mimic and miR-26b mimic negatively regulated the positive feedback between cancer cells and stromal cells and the positive feedback among stromal cells. miR-26a/-26b negatively regulated the enhanced tumorigenic potential by allergic inflammation. COX-2 was necessary for the enhanced metastatic potential of cancer cells by allergic inflammation. Taken together, our results indicate that the miR26a/-26b-COX-2-MIP-2 loop regulates allergic inflammation and the feedback relationship between allergic inflammation and the enhanced tumorigenic and metastatic potential.
authors.affiliation: From the Departments of Biochemistry and.
authors.forename: Yoojung
authors.initials: Y
authors.lastname: Kwon
authors.affiliation: From the Departments of Biochemistry and.
authors.forename: Youngmi
authors.initials: Y
authors.lastname: Kim
authors.affiliation: From the Departments of Biochemistry and.
authors.forename: Sangkyung
authors.initials: S
authors.lastname: Eom
authors.affiliation: From the Departments of Biochemistry and.
authors.forename: Misun
authors.initials: M
authors.lastname: Kim
authors.affiliation: From the Departments of Biochemistry and.
authors.forename: Deokbum
authors.initials: D
authors.lastname: Park
authors.affiliation: From the Departments of Biochemistry and.
authors.forename: Hyuna
authors.initials: H
authors.lastname: Kim
authors.affiliation: From the Departments of Biochemistry and.
authors.forename: Kyeonga
authors.initials: K
authors.lastname: Noh
authors.affiliation: Biological Sciences, College of Natural Sciences, and.
authors.forename: Hansoo
authors.initials: H
authors.lastname: Lee
authors.affiliation: the College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Yun Sil
authors.initials: YS
authors.lastname: Lee
authors.affiliation: the Graduate School of Medicine, Kangwon National University, Chunchon 200-701, Korea, and.
authors.forename: Jongseon
authors.initials: J
authors.lastname: Choe
authors.affiliation: the Graduate School of Medicine, Kangwon National University, Chunchon 200-701, Korea, and.
authors.forename: Young Myeong
authors.initials: YM
authors.lastname: Kim
authors.affiliation: From the Departments of Biochemistry and jeoungd@kangwon.ac.kr.
authors.forename: Dooil
authors.initials: D
authors.lastname: Jeoung
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry; D045744:Cell Line, Tumor; D054426:Chemokine CXCL2 / Q000378:metabolism*; D003094:Collagen / Q000737:chemistry; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004338:Drug Combinations; D005260:Female; D006967:Hypersensitivity / Q000378:metabolism; D007073:Immunoglobulin E / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism*; D007797:Laminin / Q000737:chemistry; D008168:Lung / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008546:Melanoma, Experimental; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism*; D011509:Proteoglycans / Q000737:chemistry; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; C513296:Cxcl2 protein, rat; D004338:Drug Combinations; D007797:Laminin; C556274:MIRN26 microRNA, rat; D035683:MicroRNAs; C543693:Mirn26 microRNA, mouse; D011509:Proteoglycans; D017382:Reactive Oxygen Species; C059485:matrigel; D007073:Immunoglobulin E; D003094:Collagen; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D001619:beta-N-Acetylhexosaminidases
keywords: COX-2; MIP-2; allergic inflammation; allergy; angiogenesis; metastasis; miR-26; microRNA (miRNA); tumor microenvironment; tumorigenic potential