title: CRISPR/CAS9-Mediated Genome Editing of miRNA-155 Inhibits Proinflammatory Cytokine Production by RAW264.7 Cells.
abstract: MicroRNA 155 (miR-155) is a key proinflammatory regulator in clinical and experimental rheumatoid arthritis (RA). Here we generated a miR-155 genome knockout (GKO) RAW264.7 macrophage cell line using the clustered regulatory interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (CAS9) technology. While upregulating the Src homology-2 domain-containing inositol 5-phosphatase 1 (SHIP1), the miR-155 GKO line is severely impaired in producing proinflammatory cytokines but slightly increased in osteoclastogenesis upon treatment with receptor activator of nuclear factor-κB ligand (RANKL). Taken together, our results suggest that genome editing of miR-155 holds the potential as a therapeutic strategy in RA.
authors.affiliation: Department of Medical Services, The Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Weixia
authors.initials: W
authors.lastname: Jing
authors.affiliation: Department of Rheumatology and Immunology, Clinical Immunology Center, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Xuewu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100102, China.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Rheumatology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing 100078, China.
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Hou
authors.affiliation: Department of Rheumatology & Immunology, Peking University Third Hospital, Beijing 100191, China.
authors.forename: Zhongqiang
authors.initials: Z
authors.lastname: Yao
authors.affiliation: Department of Rheumatology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing 100078, China.
authors.forename: Yuelan
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D064113:CRISPR-Cas Systems / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D055786:Gene Knockout Techniques; D016678:Genome; D006801:Humans; D000072181:Inositol Polyphosphate 5-Phosphatases; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D010010:Osteoclasts / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000096:biosynthesis / Q000235:genetics; D053245:RANK Ligand / Q000096:biosynthesis / Q000235:genetics; D017393:RNA Editing / Q000235:genetics*
chemical_list: D035683:MicroRNAs; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; C000606430:INPP5D protein, human; C000606433:Inpp5d protein, mouse; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases