論文 - 詳細
| RRC ID | 62999 |
|---|---|
| 著者 | Fu X, Song G, Ni R, Liu H, Xu Z, Zhang D, He F, Huang G. |
| タイトル | LncRNA-H19 silencing suppresses synoviocytes proliferation and attenuates collagen-induced arthritis progression by modulating miR-124a. |
| ジャーナル | Rheumatology (Oxford) |
| 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. |
| 巻・号 | 60(1) |
| ページ | 430-440 |
| 公開日 | 2021-1-5 |
| DOI | 10.1093/rheumatology/keaa395 |
| PII | 5894054 |
| PMID | 32810279 |
| MeSH | Animals Arthritis, Experimental / genetics Arthritis, Experimental / metabolism* Cell Line Cell Proliferation / genetics* Disease Progression Fibroblasts / metabolism Gene Silencing Humans Mice MicroRNAs / genetics MicroRNAs / metabolism* RNA, Long Noncoding / genetics RNA, Long Noncoding / metabolism* Synovial Membrane / metabolism Synoviocytes / metabolism* |
| IF | 5.606 |
| リソース情報 | |
| ヒト・動物細胞 | MH7A(RCB1512) |