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

Abstract

Background: Dysregulation of BZRAP1-AS1 was associated with immune statuses of cancer or Alzheimer's disease patients, yet little is known about its role in rheumatoid arthritis.Methods: RT-qPCR and western blot were applied to assess the expression of indicated expression. CCK-8 and BrdU proliferation assays were used to measure the proliferation of RA-HFLS. Apoptosis in RA-HFLS was evidenced by the alteration of caspase-3 activity and apoptosis-related factors. ELISA was performed to detect IL-6, IL-1β, and TNF-α level. Luciferase reporter, RIP, and pull-down assays were used to confirm the BZRAP1-AS1/miR-1286/COL5A2 cascade predicted by bioinformatics analysis.Results: BZRAP1-AS1 and COL5A2 were downregulated in RA tissues and RA-HFLS while miR-1286 was amplified. Overexpression of BZRAP1-AS1 reduced the RA-HFLS proliferation, IL-6, IL-1β, and TNF-α level and induced cell apoptosis while BZRAP1-AS1 silence produced an opposite effect. Overexpression of BZRAP1-AS1 reduced the miR-1286 expression which in turn increased the COL5A2 expression, thereby relieving the excessive proliferation and limited apoptosis in RA-HFLS. Conclusion:Our findings suggested that BZRAP1-AS1 sequestered miR-1286 and reshaped the COL5A2 expression, thereby suppressed RA-HFLS proliferation and inflammation, and triggered cell apoptosis, resulting in the attenuation of RA progression.

Long noncoding RNA/circular RNA regulates competitive endogenous RNA networks in rheumatoid arthritis: molecular mechanisms and traditional Chinese medicine therapeutic significances

“…Moreover, CircFADS2 could mediate mTOR expression via binding to miR-498, and CircFADS2 stimulated mitophagy via the miR-498/mTOR axis [ 71 ]. Furthermore, lncRNA OIP5-AS1/miR-448/TLR3/NF-κB, lncRNA BZRAP1-AS1/miR-1286/COL5A2 and LncRNA XIST/miR-126-3p/NF-κB have been found to strengthen proliferation and restrict apoptosis of RA-FLS [ 49 , 54 , 58 ].…”