LINC00475在滑膜成纤维细胞中的调控作用及其与类风湿性关节炎进展的相关性<sup>*</sup>

doi:10.3969/j.issn.1671-7171.2026.02.001

摘要
图/表
参考文献
相关文章 (15)

全文: PDF (2130 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

摘要 【目的】 探讨LINC00475在滑膜成纤维细胞(SFs)中的调控作用及其与类风湿性关节炎(RA)进展的相关性。【方法】 选择2019年2月至2020年2月在湖南省人民医院行膝关节手术的60例患者,根据疾病类型不同将患者分为RA组(RA患者,n=30)和对照组(无关节疾病的半月板损伤患者,n=30)。对其中SFs进行分离、培养、增殖与转染,并采用双荧光素酶报告基因检测、免疫荧光染色、Western blot分析等方法对SFs凋亡与目标调节因子的相关性进行分析。【结果】 RA组滑膜组织中LINC00475表达水平显著高于对照组,差异有统计学意义(P<0.05)。RA组滑膜组织中miR-27b-3p表达水平低于对照组,差异有统计学意义(P<0.05)。相关性分析显示,LINC00475表达水平升高与RA病情进展情况呈正相关(P<0.05)。Western blot结果显示,RA组滑膜组织中RC3H1表达显著高于对照组(P<0.05)。双荧光素酶基因实验显示,LINC00475与miR-27b-3p、miR-27b-3p与RC3H1存在直接相互作用。免疫荧光染色、Western blot、qRT-PCR结果均显示,LINC00475-WT组SFs中RC3H1表达水平显著高于LINC00475突变组及对照组(P<0.05)。Western blot和qRT-PCR结果显示:与对照组及转染对照组相比,LINC00475过表达组和miR-27b-3p低表达组的RC3H1表达水平显著降低(P<0.05);LINC00475低表达组和miR-27b-3p高表达组的RC3H1表达水平升高(P<0.05)。免疫荧光结果显示,LINC00475过表达与miR-27b-3p敲低均上调了RC3H1的表达强度,其中LINC00475过表达组呈现更显著的上调效应。细胞增殖实验显示:与对照组相比,LINC00475或RC3H1过表达均可促进SFs增殖;敲低LINC00475或RC3H1则显著抑制SFs增殖。【结论】 LINC00475作为竞争性内源性RNA通过吸附miR-27b-3p,促进RC3H1基因高表达,诱导SFs自噬,抑制SFs凋亡,最终导致SFs增殖异常,从而加剧RA的进展。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	何励伟
	谭宇轩
	郭宇鹏
	黄术
	周益昭

关键词 ： RNA,长链非编码, 关节炎,类风湿, 自噬

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.

Key words： RNA, Long Noncoding Arthritis, Rheumatoid Autophagy

收稿日期: 2025-10-30

中图分类号:

R593.22

基金资助:^*湖南省自然科学基金面上项目(项目编号:S2021JJMSXM0834);湖南省教育厅科研项目(项目编号20C1149);湖南省教育厅重点课题(项目编号:23A0097)

通讯作者: ^**E-mail:7329406@qq.com

引用本文:

何励伟, 谭宇轩, 郭宇鹏, 黄术, 周益昭. LINC00475在滑膜成纤维细胞中的调控作用及其与类风湿性关节炎进展的相关性^*[J]. 医学临床研究, 2026, 43(2): 177-181.
HE Liwei, TAN Yuxuan, GUO Yupeng, HUANG Shu, ZHOU Yizhao. The Regulatory Role of LINC00475 in Synovial Fibroblasts and its Correlation with the Progression of Rheumatoid Arthritis. JOURNAL OF CLINICAL RESEARCH, 2026, 43(2): 177-181.

链接本文:

http://journal07.magtech.org.cn/yxlcyj/CN/10.3969/j.issn.1671-7171.2026.02.001 或 http://journal07.magtech.org.cn/yxlcyj/CN/Y2026/V43/I2/177

[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.