LncRNA-H19 silencing suppresses synoviocytes proliferation and attenuates collagen-induced arthritis progression by modulating miR-124a. (18th August 2020)

• Record Type: Journal Article
• Authors: Fu, Xiaohong; Song, Guojing; Ni, Rongrong; Liu, Han; Xu, Zhizhen; Zhang, Dinglin; He, Fengtian; Huang, Gang
• Is Part Of: Rheumatology. Volume 60:Number 1(2021)
• Page Start: 430
• Page End: 440
• Publication Date: 2020-08-18
• Subjects: fibroblast-like synoviocytes -- lncRNA-H19 -- miR-124a -- Liver X receptor -- CDK2 -- MCP-1; Rheumatism -- Periodicals; Rheumatology -- Periodicals; 616.723005
• DOI: 10.1093/rheumatology/keaa395
• Languages: English
• ISSNs: 1462-0324

Abstract

Abstract: Objectives: Long non-coding RNA H19 (lncRNA-H19) is highly expressed in fibroblast-like synoviocytes (FLS) from patients with RA. The present study aimed to clarify the pathological significance and regulatory mechanisms of lncRNA-H19 in FLS. Methods: Mice with CIA were locally injected with LV-shH19. The progression of CIA was explored by measuring arthritic index (AI), paw thickness (PT) and histologic analysis. The growth and cell cycle of human synoviocyte MH7A were assessed by CCK-8 and flow cytometric analysis. The putative binding sites between lncRNA-H19 and miR-124a were predicted online, and the binding was identified by luciferase assay. RT-qPCR, Western blot and luciferase assay were performed to explore the molecular mechanisms between liver X receptor (LXR), lncRNA-H19, miR-124a and its target genes. Results: The expression of lncRNA-H19 was closely associated with the proliferation of synoviocytes and knockdown of lncRNA-H19 significantly ameliorated the progression of CIA, reflected by decreased AI, PT and cartilage destruction. Notably, lncRNA-H19 competitively bound to miR-124a, which directly targets CDK2 and MCP-1. It was confirmed that lncRNA-H19 regulates the proliferation of synoviocytes by acting as a sponge of miR-124a to modulate CDK2 and MCP-1 expression. Furthermore, the agonists of LXR inhibited lncRNA-H19-mediated miR-124a-CDK2/MCP-1 signalling pathway in synoviocytes. The 'lncRNA-H19-miR-124a-CDK2/MCP-1' axis plays an important role in LXR anti-arthritis. Conclusion: Regulation of the miR-124a-CDK2/MCP-1 pathway by lncRNA-H19 plays a crucial role in the proliferation of FLS. Targeting this axis has therapeutic potential in the treatment of RA and may represent a novel strategy for RA treatment.