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| The Regulatory Role of LINC00475 in Synovial Fibroblasts and its Correlation with the Progression of Rheumatoid Arthritis |
| HE Liwei1, TAN Yuxuan1, GUO Yupeng1, HUANG Shu1,2, ZHOU Yizhao1,2 |
1. The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital),Changsha Hunan 410005;
2. Clinical Research Center of Sports Medicine in Hunan Province,Changsha Hunan 410005 |
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Abstract 【Objective】 To explore the regulatory role of LINC00475 in synovial fibroblasts (SFs) and its correlation with the progression of rheumatoid arthritis (RA). 【Methods】 A total of 60 patients who underwent knee joint surgery in Hunan Provincial People's Hospital from February 2019 to February 2020 were selected. According to different disease types, the patients were divided into the RA group (RA patients, n=30) and the control group (patients with meniscus injury without joint disease, n=30). SFs were isolated, cultured, proliferated and transfected, and the relationship between SFs apoptosis and target regulatory factors was analyzed by dual-luciferase reporter gene assay, immunofluorescence staining, Western blot analysis and other methods. 【Results】 The expression level of LINC00475 in synovial tissue of the RA group was significantly higher than that of the control group, and the difference was statistically significant (P<0.05). The expression level of miR-27b-3p in synovial tissue of the RA group was lower than that of the control group, and the difference was statistically significant (P<0.05). Correlation analysis showed that the increased expression level of LINC00475 was positively correlated with the progression of RA (P<0.05). Western blot results showed that the expression of RC3H1 in synovial tissue of RA patients was significantly higher than that in the normal group (P<0.05). Dual-luciferase reporter gene assay showed that there was a direct interaction between LINC00475 and miR-27b-3p, as well as between miR-27b-3p and RC3H1. The results of immunofluorescence staining, Western blot and qRT-PCR all showed that the expression level of RC3H1 in SFs of the LINC00475-WT group was significantly higher than that of the LINC00475 mutant group and the control group (P<0.05). Western blot and qRT-PCR results showed that compared with the normal group and the transfection control group, the expression level of RC3H1 in the LINC00475 overexpression group and the miR-27b-3p low expression group was significantly decreased (P<0.05); the expression level of RC3H1 in the LINC00475 low expression group and the miR-27b-3p high expression group was increased (P<0.05). Immunofluorescence results showed that both LINC00475 overexpression and miR-27b-3p knockdown upregulated the expression intensity of RC3H1, and the LINC00475 overexpression group showed a more significant upregulation effect. Cell proliferation assay showed that compared with the control group, overexpression of LINC00475 or RC3H1 could promote the proliferation of SFs; knockdown of LINC00475 or RC3H1 significantly inhibited the proliferation of SFs. 【Conclusion】 As a competing endogenous RNA, LINC00475 promotes the high expression of RC3H1 gene by adsorbing miR-27b-3p, induces SFs autophagy, inhibits SFs apoptosis, and ultimately leads to abnormal proliferation of SFs, thereby accelerating the progression of RA.
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Received: 30 October 2025
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[1] PETRELLI F, MARIANI F M, ALUNNO A, et al. Pathogenesis of rheumatoid arthritis: one year in review 2022[J].Clin Exp Rheumatol,2022,40(3):475-482.
[2] KARAMI J, ASLANI S, TAHMASEBI M N, et al. Epigenetics in rheumatoid arthritis; fibroblast-like synoviocytes as an emerging paradigm in the pathogenesis of the disease[J].Immunol Cell Biol,2020,98(3):171-186.
[3] KLEIN K, GAY S. Epigenetics in rheumatoid arthritis[J].Curr Opin Rheumatol,2015,27(1):76-82.
[4] KOMATSU N, TAKAYANAGI H. Mechanisms of joint destruction in rheumatoid arthritis-immune cell-fibroblast-bone interactions[J].Nat Rev Rheumatol,2022,18(7):415-429.
[5] KIM E K, KWON J E, LEE S Y, et al. IL-17-mediated mitochondrial dysfunction impairs apoptosis in rheumatoid arthritis synovial fibroblasts through activation of autophagy[J].Cell Death Dis,2017,8(1) :e2565.
[6] KATO M, OSPELT C, GAY R E, et al. Dual role of autophagy in stress-induced cell death in rheumatoid arthritis synovial fibroblasts[J].Arthritis Rheumatol,2014,66(1):40-48.
[7] VOMERO M, BARBATI C, COLASANTI T, et al. Alessandri, autophagy and rheumatoid arthritis: current knowledges and future perspectives[J].Front Immunol,2018,9:1577.
[8] ALETAHA D,NEOGI T,SILMAN A J, et al.2010 Rheumatoid arthritis classification criteria:An American College of Rheumatology/European League Against Rheumatism collaborative initiative[J].Ann Rheum Dis,2010, 69(9):1580-1588.
[9] WANG J, ZHAO Q. Expression of CCR3, SOX5 and LC3 in patients with elderly onset rheumatoid arthritis and the clinical significance[J].Exp Ther Med, 2017,14(4):3573-3576.
[10] MICHEROLI R, ELHAI M, EDALAT S, et al. Role of synovial fibroblast subsets across synovial pathotypes in rheumatoid arthritis: a deconvolution analysis[J].RMD Open,2022,8(1):e001949.
[11] ZHU J J, FU H J, WU Y G, et al. Function of lncRNAs and approaches to lncRNA-protein interactions[J].Sci China Life Sci,2013,56(10):876-885.
[12] LIU Y B, LIN L P, ZOU R, et al. MSC-derived exosomes promote proliferation and inhibit apoptosis of chondrocytes via lncRNA-KLF3-AS1/miR-206/GIT1 axis in osteoarthritis[J].Cell Cycle,2018,17(21-22):2411-2422.
[13] ESSIG K, HU D, GUIMARAES J C, et al. Roquin suppresses the PI3K-mTOR signaling pathway to inhibit T helper cell differentiation and conversion of treg to Tfr cells[J].Immunity,2017,47(6):1067-1082.
[14] MCINNES I B, SCHETT G. The pathogenesis of rheumatoid arthritis[J].N Engl J Med,2011,365(23): 2205-2219.
[15] HUANG W T, LI X, HUANG C, et al. LncRNAs and rheumatoid arthritis: from identifying mechanisms to clinical investigation[J].Front Immunol,2022,12:807738.
[16] RADU A F, BUNGAU S G. Management of rheumatoid arthritis: an overview[J].Cells,2021,10(11):2857. |
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2026, Vol. 43 
