title: Dysregulation of the miR-324-5p-CUEDC2 axis leads to macrophage dysfunction and is associated with colon cancer.
abstract: CUEDC2, a CUE-domain-containing protein, modulates inflammation, but its involvement in tumorigenesis is still poorly understood. Here, we report that CUEDC2 is a key regulator of macrophage function and critical for protection against colitis-associated tumorigenesis. CUEDC2 expression is dramatically upregulated during macrophage differentiation, and CUEDC2 deficiency results in excessive production of proinflammatory cytokines. The level of CUEDC2 in macrophages is modulated by miR- 324-5p. We find that Cuedc2 KO mice are more susceptible to dextran-sodium-sulfate-induced colitis, and macrophage transplantation results suggest that the increased susceptibility results from the dysfunction of macrophages lacking CUEDC2. Furthermore, we find that Cuedc2 KO mice are more prone to colitis-associated cancer. Importantly, CUEDC2 expression is almost undetectable in macrophages in human colon cancer, and this decreased CUEDC2 expression is associated with high levels of interleukin-4 and miR-324-5p. Thus, CUEDC2 plays a crucial role in modulating macrophage function and is associated with both colitis and colon tumorigenesis.
authors.affiliation: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing 100850, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing 100850, China; Department of Digestive, Navy General Hospital, 6 Fucheng Road, Beijing 100048, China.
authors.forename: Shao-Xin
authors.initials: SX
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing 100850, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Mu
authors.affiliation: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing 100850, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing 100850, China.
authors.forename: Zhao-Shan
authors.initials: ZS
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing 100850, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Liang
authors.affiliation: Department of Transfusion Medicine, Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100071, China.
authors.forename: Hai-Long
authors.initials: HL
authors.lastname: Zhuo
authors.affiliation: Department of General Surgery, Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100071, China.
authors.forename: Xiao-Peng
authors.initials: XP
authors.lastname: Hao
authors.affiliation: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing 100850, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing 100850, China.
authors.forename: Di-Feng
authors.initials: DF
authors.lastname: Fang
authors.affiliation: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing 100850, China.
authors.forename: Zhao-Fang
authors.initials: ZF
authors.lastname: Bai
authors.affiliation: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing 100850, China.
authors.forename: Qian-Yi
authors.initials: QY
authors.lastname: Wang
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, 27 Tai-Ping Road, Beijing 100850, China.
authors.forename: He-Mei
authors.initials: HM
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing 100850, China.
authors.forename: Bao-Feng
authors.initials: BF
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing 100850, China.
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Gong
authors.affiliation: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing 100850, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing 100850, China.
authors.forename: Xue-Min
authors.initials: XM
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing 100850, China. Electronic address: qxia@ncba.ac.cn.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing 100850, China. Electronic address: tli@ncba.ac.cn.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003092:Colitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C519556:CUEDC2 protein, human; C576361:CUEDC2 protein, mouse; D002352:Carrier Proteins; D008565:Membrane Proteins; D035683:MicroRNAs; D012097:Repressor Proteins