Table 1.
Studies included
| Study | Small interfering RNA target gene* | Function of RA therapy | Drugs activity tested | Cells analyzed | Type of study |
|---|---|---|---|---|---|
| Lee et al. 21 | HIF-1α | HIF-1α is used to monitor the effect of hypoxia on the inflammatory process | HIF-1α – siRNA | Fibroblasts | in vitro |
| Ikuta et al. 16 | Sp1 | Sp1 inhibits GLS, which has angiogenic and arthritogenic activities | Mithramycin | FLS | in vitro |
| Park et al. 17 | COX-2 | COX-2 is implicated in the inflammatory response | Dexamethasone, COX-2-siRNA | Chondrocyte | in vitro |
| Li et al. 18 | HMGB1 | HMGB1 is associated with the development of RA. | MTX | FLS | in vitro |
| Municio et al. 19 | TS | TS acts on p53 therefore on macrophage activity | MTX | Macrophages | in vivo |
| Xu et al. 23 | Cyr61 | Cyr61 acts on matrix MMP-3 and MMP-13, mediates cell adhesion, migration and cell apoptosis in inflammatory processes of RA | Cyr61-siRNA | FLS | in vitro |
| Chen et al. 22 | PRMT5 | PRMT5 regulate inflammation, cell proliferation, migration and invasion of FLSs | PRMT5-siRNA | FLS | in vitro |
| Nogueira et al. 24 | Mcl-1 | Mcl-1 is a protein essential for synovial macrophage survival | MCL1 siRNA | Macrophages | in vitro |
| Wang et al. 25 | RRM2 | RRM2 is a critical protein for DNA synthesis and repair, which promotes the proliferation of cells and inhibits cellular apoptosis. | RRM2 siRNA | FLS | in vitro |
| Li et al. 33 | STAT3 | STAT3 modulates the signaling of Th17 transcription, transduction and activation present in the RA | As2O3 | Th17 | in vitro |
| Ma et al. 34 | PDK-1 | PDK-1 stimulates invasion and migration of FLS from RA patients | Artesunate | FLS | in vitro |
| Peng et al. 14 | COX-2 | COX-2 is involved in the inflammatory response via some mediators, including TREM-1 | COX-2-siRNA | Monocytes/macrophages, lymphocytes and mast cells | in vitro |
| Yu Du et al. 26 | Nrf2 | FLS increased the level of reactive intracellular oxygen species via TNF-α | Nrf2-siRNA | FLS | in vitro |
| Choi et al. 28 | EGR3 | EGR3 promotes Cyr61-induced cell migration and invasion | EGR3-siRNA | FLS | in vitro |
| Wakabayashi et al. 29 | CCL11 | CCL11 induces the migration of different leukocyte types by interacting with CCR3 | CCL11-siRNA | FLS, monocytes | in vitro |
| Xu et al. 30 | E2F2 | E2F is involved in cell proliferation and survival, cell signaling and cell cycle regulation | E2F2-siRNA | FLS | in vitro |
| Wang et al. 27 | SphK1 | SphK1 is involved in the angiogenesis process via VEGF | SphK1-siRNA | FLS | in vitro |
| Saruga et al. 15 | MDA5 | MDA5 is an RNA helicase that plays a role in innate immune and inflammatory reactions | MDA5-siRNA | FLS | in vitro |
| Zhao et al. 32 | RANKL | RANKL is the most important inducer of osteoclastogenesis and is expressed and upregulated in the synovial tissues of the RA | RANKL-siRNA | Synovial cells | in vitro |
| Yoon and Moon31 | hBAFF | hBAFF regulates the maturation, maintenance and apoptosis of B cells | hBAFF-siRNA | FLS | in vitro |
*HIF-1α, Hypoxia-inducible factor-1α; Sp1, Specificity protein 1; COX-2, Cyclooxygenase-2; PRMT5, Protein arginine methyltransferase 5; HMGB1, High-mobility group box 1; TS, Thymidylate synthase; Cyr61, Cysteine-rich protein 61; Mcl-1, Myeloid cell leukemia-1; RRM2, Ribonucleotide reductase M2; STAT3, Signal transducer and activator of transcription 3; PDK-1, Phosphoinositide-dependent kinase-1; Nrf2, Nuclear factor erythroid 2-related factor 2; EGR3, Early growth response 3; CCL11, Chemokine C–C motif ligand 11; E2F2, E2F transcription factor 2; SphK1, Sphingosine kinase-1; MDA5, Melanoma differentiation-associated gene 5; RANKL, Receptor activator of nuclear factor κB ligand; hBAFF, B cell-activating factor.