title: MicroRNA-663 activates the canonical Wnt signaling through the adenomatous polyposis coli suppression.
abstract: Rheumatoid arthritis (RA) is a symmetrical polyarticular autoimmune disease of unknown etiology. In this present study, we observed that the adenomatous polyposis coli (APC) expression is down-regulated and the expression of microRNA (miR)-663 increased significantly in synovium from RA patients compared with control. Target gene prediction for miR-663 revealed that the mRNA of APC gene, which is a member of the canonical Wnt signaling pathway, has a miR-663 binding site in its 3'-untranslated region (3'UTR). The result showed that increased miR-663 suppressed the APC expression significantly, and this down-regulation of APC expression triggered the activation of canonical Wnt signaling through accumulation of β-catenin in fibroblast-like synoviocytes (FLS). In addition, increased miR-663 induced the FLS proliferation and the expression MMP3 and fibronectin during disease development. Therefore, miR-663 can be considered as a critical regulator of RA pathogenesis and can be utilized for developing miRNA-based therapeutic agents for RA patients.
authors.affiliation: School of Food and Drug, Anhui Key Laboratory of Poultry Epidemic Prevention and Surveillance, Anhui Science and Technology University, Fengyang 233100, China; School of Pharmacy, Anhui Medical University, Hefei 230032, China.
authors.forename: Cheng-gui
authors.initials: CG
authors.lastname: Miao
authors.affiliation: School of Food and Drug, Anhui Key Laboratory of Poultry Epidemic Prevention and Surveillance, Anhui Science and Technology University, Fengyang 233100, China.
authors.forename: Wei-jing
authors.initials: WJ
authors.lastname: Shi
authors.affiliation: School of Food and Drug, Anhui Key Laboratory of Poultry Epidemic Prevention and Surveillance, Anhui Science and Technology University, Fengyang 233100, China.
authors.forename: You-yi
authors.initials: YY
authors.lastname: Xiong
authors.affiliation: School of Food and Drug, Anhui Key Laboratory of Poultry Epidemic Prevention and Surveillance, Anhui Science and Technology University, Fengyang 233100, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yu
authors.affiliation: School of Food and Drug, Anhui Key Laboratory of Poultry Epidemic Prevention and Surveillance, Anhui Science and Technology University, Fengyang 233100, China.
authors.forename: Xiao-lin
authors.initials: XL
authors.lastname: Zhang
authors.affiliation: School of Food and Drug, Anhui Key Laboratory of Poultry Epidemic Prevention and Surveillance, Anhui Science and Technology University, Fengyang 233100, China.
authors.forename: Mei-song
authors.initials: MS
authors.lastname: Qin
authors.affiliation: School of Food and Drug, Anhui Key Laboratory of Poultry Epidemic Prevention and Surveillance, Anhui Science and Technology University, Fengyang 233100, China.
authors.forename: Chuan-lai
authors.initials: CL
authors.lastname: Du
authors.affiliation: Affiliated Hospital, Bengbu Medical College, Bengbu 233000, China.
authors.forename: Tong-wen
authors.initials: TW
authors.lastname: Song
authors.affiliation: First Affiliated Hospital, Anhui Medical University, Hefei 230032, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei 230032, China. Electronic address: lijunamu@126.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D025601:Adenomatous Polyposis Coli Protein / Q000096:biosynthesis / Q000235:genetics*; D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000473:pathology; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation; D005260:Female; D005353:Fibronectins / Q000096:biosynthesis; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000235:genetics*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D025601:Adenomatous Polyposis Coli Protein; C508606:CXCL8 protein, human; D005353:Fibronectins; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; C552243:MIRN663 microRNA, human; D035683:MicroRNAs; D051176:beta Catenin; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3
keywords: Adenomatous polyposis coli; Canonical Wnt signaling pathway; Fibroblast-like synoviocytes; Rheumatoid arthritis; microRNA-663