lncRNA CASC2 downregulation participates in rheumatoid arthritis, and CASC2 overexpression promotes the apoptosis of fibroblast‑like synoviocytes by downregulating IL‑17

Abstract

lncrna cancer susceptibility candidate 2 (caSc2) is a recently identified oncogenic lncRNA in different types of cancers. Our preliminary microarray data showed that lncRNA CASC2 was downregulated in the plasma of patients with rheumatoid arthritis (RA), indicating the involvement of this lncRNA in RA. In the present study, lncRNA CASC2 and IL-17 in plasma were detected by reverse transcription-quantitative PCR and ELISA, respectively. Diagnostic analyses were performed using receiver operating characteristic curves. Flow cytometry was performed to evaluate cell apoptosis. The effects of lncRNA CASC2 on IL-17 expression were determined via western blotting. lncRNA CASC2 was found to be downregulated, while IL-17 was upregulated in the plasma of RA patients when compared with these levels in the plasma of healthy controls. Plasma levels of lncRNA CASC2 and IL-17 were significantly and inversely correlated in both RA patients and healthy controls. Altered plasma levels of lncRNA CASC2 and IL-17 were able to differentiate RA patients from healthy controls. Overexpression of lncRNA CASC2 promoted, while treatment with IL-17 inhibited the apoptosis of human fibroblast-like synoviocytes (HFLSs) isolated from RA patients. Overexpression of lncRNA CASC2 inhibited IL-17 expression in HFLS, while treatment with IL-17 did not significantly affect the expression of lncRNA CASC2. Therefore, downregulation of lncRNA CASC2 is involved in RA and lncRNA CASC2 overexpression may promote the apoptosis of HFLS by downregulating IL-17.

lncRNA BZRAP1‐AS1 alleviates rheumatoid arthritis by regulating miR‐1286/COL5A2 axis

“…24 Currently, lncRNAs reportedly modulate HFLS cells survival and cell growth, and the inflammatory response during RA progression. 25 Herein, BZRAP1-AS1 competitively binds to an effective miR-1286 sponge and increases the expression of the miR-1286 target, COL5A2, thereby impedes RA progression. Initially, BZRAP1-AS1 showed lower expression in RA synovial tissues and RA-HFLS, in comparison with the normal synovial samples and normal HFLS cells, respectively, highlighting its potential implication in RA progression.…”

“… 24 Currently, lncRNAs reportedly modulate HFLS cells survival and cell growth, and the inflammatory response during RA progression. 25 Herein, BZRAP1‐AS1 competitively binds to an effective miR‐1286 sponge and increases the expression of the miR‐1286 target, COL5A2, thereby impedes RA progression.…”

“…Hyperplastic HFLS cells not only excrete various proinflammatory cytokines, chemokines, and growth factors but also possesses transforming properties, which contributes to bone and cartilage erosion and aggravates disease manifestations 24 . Currently, lncRNAs reportedly modulate HFLS cells survival and cell growth, and the inflammatory response during RA progression 25 . Herein, BZRAP1‐AS1 competitively binds to an effective miR‐1286 sponge and increases the expression of the miR‐1286 target, COL5A2, thereby impedes RA progression.…”

A Novel Regulatory Player in the Innate Immune System: Long Non-Coding RNAs

“…Moreover, Hotair activates MMP-2 and MMP-13 in osteoclasts and synoviocytes, which may lead to proteinase-mediated dissolution of articular cartilage matrix and subchondral bone resorption during RA pathogenesis. In contrast, lncRNA CASC2 is downregulated in the plasma of RA patients [161]. Through decreasing IL-17 expression, CASC2 could potently promote the apoptosis of FLSs that contribute to RA development by producing cytokines and proteases [161].…”

“…In contrast, lncRNA CASC2 is downregulated in the plasma of RA patients [161]. Through decreasing IL-17 expression, CASC2 could potently promote the apoptosis of FLSs that contribute to RA development by producing cytokines and proteases [161]. However, due to the complicated pathogenic mechanism of autoimmune disease, there is extensive lncRNA regulatory potential that has yet to be discovered in RA development.…”