Rheumatoid Arthritis

ZFAS1[LncRNA]

miR-296-5p[miRNA]

MMP-15[mRNA]

TNF-α-stimulated MH7A cells

Mus musculus (mouse)

Int Immunopharmacol. 2021 Jan;90:107061. doi: 10.1016/j.intimp.2020.107061. Epub 2020 Nov 13.

Long noncoding RNA ZFAS1 silencing alleviates rheumatoid arthritis via blocking miR-296-5p-mediated down-regulation of MMP-15.

Dual-luciferase reporter assay;RNA immunoprecipitation;Luciferase reporter assay;RNA immunoprecipitation;

Rheumatoid arthritis (RA), a chronic inflammatory disease, deprives patients' walking ability and reduces their life quality worldwide. Though recent studies have indicated the role of long noncoding RNA (lncRNA) ZFAS1 in several diseases, however, its role in RA remains uncharacterized. The present study aimed to unravel the the effect of ZFAS1 on RA. Herein, the RA mouse model and the human RA synoviocyte MH7A cell lines stimulated with TNF-α were established. ZFAS1 was next determined to be highly expressed in the mice with RA-like symptoms and TNF-α-stimulated MH7A cells while inhibiting ZFAS1 was demonstrated to promote proliferation and suppress apoptosis of MH7A cells. Furthermore, ZFAS1 knockdown exerted anti-inflammation effect in vitro and in vivo and reduced the arthritis index value. Moreover, RNA immunoprecipitation and dual-luciferase reporter assays identified the binding of ZFAS1 to microRNA (miR)-296-5p as well as the binding of miR-296-5p to matrix metalloproteinase-15 (MMP-15). Of note, ZFAS1 could bind miR-296-5p to up-regulate the expression of MMP-15. Our results from in vitro and in vivo experiments demonstrated silencing ZFAS1 mitigated RA-like symptoms such as inflammation and hyperplasia via miR-296-5p-dependent inhibition of MMP-15. Taken altogether, our study confirmed that ZFAS1 involved in RA progression by competitively binding to miR-296-5p and regulating MMP-15 expression.