title: Downregulation of microRNA‑221 decreases migration and invasion in fibroblast‑like synoviocytes in rheumatoid arthritis.
abstract: MicroRNAs (miRNAs/miRs) are a group of non-coding RNAs that regulate the activity of target mRNAs and cellular processes, and which have been implicated in the pathogenesis of autoimmune diseases. miR-221 is one of the miRNAs that regulate cell proliferation, invasion and apoptosis in tumors. However, the role of miR-221 in rheumatoid arthritis (RA) remains to be fully elucidated. Therefore, the present study was undertaken to identify the role of miR-221 in RA. The expression of miR-221 in serum and synovial tissues of patients with RA and healthy controls was confirmed by reverse transcription quantitative polymerase chain reaction analysis. The effects of miR-221 on pro-inflammatory cytokines and a chemokine were assessed by ELISA. The effects of miR-221 on cell apoptosis, migration and invasion in fibroblast-like synoviocytes (FLS) were also assessed in vitro. The results showed that miR-221 expression in serum and synovial tissues of patients with RA was higher than that in healthy controls. Downregulation of miR-221 significantly suppressed the expression of pro-inflammatory cytokines and the chemokine, and inhibited FLS cell migration and invasion via inhibiting vascular endothelial growth factor, matrix metalloproteinase (MMP)-3 and MMP-9 expression. In addition, downregulation of miR-221 significantly induced cell apoptosis and decreased survivin and X-linked inhibitor of apoptosis protein expression. These findings indicated that downregulation of miR-221 inhibited the expression of pro-inflammatory cytokines and the chemokine, suppressed FLS cell migration and invasion, and induced cell apoptosis. Therefore, miR-221 is likely to be implicated in RA pathogenesis via these mechanisms, and may be a target for the treatment of RA.
authors.affiliation: Department of Orthopaedics, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Shuzhong
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Orthopaedics, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Yougeng
authors.initials: Y
authors.lastname: Yang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051116:Receptors, Scavenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; D035683:MicroRNAs; D034741:RNA, Small Interfering; D051116:Receptors, Scavenger; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C423727:CXCL16 protein, human; C508600:IL6 protein, human; C525709:MIR221, human; C467484:VEGFA protein, human