[1]王峰,杨雯娣,张林,等.环状RNA NOLC1和miR-708-5p对类风湿关节炎滑膜成纤维细胞的影响及其作用机制研究[J].中医正骨,2026,38(02):23-32,41.
　WANG Feng,YANG Wendi,ZHANG Lin,et al.Research on the effects of circular RNA NOLC1 and miR-708-5p on rheumatoid arthritis synovial fibroblasts and their mechanisms of action[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2026,38(02):23-32,41.
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环状RNA NOLC1和miR-708-5p对类风湿关节炎滑膜成纤维细胞的影响及其作用机制研究()

《中医正骨》[ISSN:1001-6015/CN:41-1162/R]

卷:
第38卷
期数:
2026年02期
页码:
23-32,41
栏目:
基础研究
出版日期:
2026-02-20

文章信息/Info

Title:
Research on the effects of circular RNA NOLC1 and miR-708-5p on rheumatoid arthritis synovial fibroblasts and their mechanisms of action
作者:
王峰; 杨雯娣; 张林; 刘高瞻
襄阳市中心医院,湖北 襄阳 441021
Author(s):
WANG Feng; YANG Wendi; ZHANG Lin; LIU Gaozhan
Xiangyang Central Hospital, Xiangyang 441021, Hubei, China
关键词:
关节炎; 类风湿;  滑膜;  成纤维细胞;  环状RNA NOLC1;  miR-708-5p;  细胞活性;  细胞增殖;  细胞迁移;  细胞侵袭
Keywords:
arthritis; rheumatoid;  synovial membrane;  fibroblasts;  circular RNA NOLC1;  miR-708-5p;  cell viability;  cell proliferation;  cell migration;  cell invasion
摘要:
目的:探讨环状RNA NOLC1(circular RNA NOLC1,circNOLC1)和miR-708-5p对类风湿关节炎(rheumatoid arthritis,RA)滑膜成纤维细胞的影响及其作用机制。方法:①RA滑膜成纤维细胞的获取方法。取晚期RA患者滑膜组织,分离、培养获得RA滑膜成纤维细胞。②抑制circNOLC1表达对RA滑膜成纤维细胞影响的分析方法。将RA滑膜成纤维细胞分为阴性对照组和 circNOLC1抑制组,分别转染非靶向干扰小RNA(small interfering RNA,siRNA)和靶向circNOLC1的siRNA; 培养48 h后,检测各组细胞的circNOLC1表达水平、细胞活性、细胞增殖能力(细胞克隆数)、细胞迁移能力(划痕愈合率)、细胞侵袭能力(侵袭细胞数)及上皮钙黏蛋白和神经钙黏蛋白表达水平。③过表达miR-708-5p对RA滑膜成纤维细胞影响的分析方法。将RA滑膜成纤维细胞分为阴性对照组和miR-708-5p过表达组,分别转染miR-708-5p模拟物阴性对照物和miR-708-5p模拟物; 培养48 h后,检测各组细胞的miR-708-5p表达水平、细胞活性、细胞增殖能力(细胞克隆数)、细胞迁移能力(划痕愈合率)、细胞侵袭能力(侵袭细胞数)及上皮钙黏蛋白和神经钙黏蛋白表达水平。④抑制circNOLC1和miR-708-5p表达对RA滑膜成纤维细胞影响的分析方法。将RA滑膜成纤维细胞分为阴性对照组与circNOLC1和miR-708-5p联合抑制组,阴性对照组采用转染靶向circNOLC1的siRNA和miR-708-5p抑制剂阴性对照物,circNOLC1和miR-708-5p联合抑制组转染靶向circNOLC1的siRNA和miR-708-5p抑制剂; 培养48 h后,检测各组细胞的各项指标(同③)。⑤miR-708-5p与circNOLC1预测靶位点结合的验证方法。将RA滑膜成纤维细胞分为阴性对照组和miR-708-5p过表达组,每组再分为野生型亚组和突变型亚组。阴性对照组的野生型亚组转染miR-708-5p模拟物阴性对照物和野生型circNOLC1 psiCHECK-2重组载体,突变型亚组转染miR-708-5p模拟物阴性对照物和突变型circNOLC1 psiCHECK-2重组载体; miR-708-5p过表达组的野生型亚组转染miR-708-5p模拟物和野生型circNOLC1 psiCHECK-2重组载体,突变型亚组转染miR-708-5p模拟物和突变型circNOLC1 psiCHECK-2重组载体。培养48 h后,检测各组RA滑膜成纤维细胞的相对荧光素酶活性。⑥circNOLC1与miR-708-5p在Ago2复合物中共富集的验证方法。将RA滑膜成纤维细胞分为抗免疫球蛋白G(immunoglobulin,IgG)抗体组和抗Ago2抗体组,裂解细胞后将抗IgG抗体包被的磁珠和抗Ago2抗体包被的磁珠分别加入抗IgG抗体组和抗Ago2抗体组的细胞裂解液中孵育,收集磁珠检测circNOLC1和miR-708-5p水平。⑦circNOLC1与miR-708-5p靶向物理结合的验证方法。将RA滑膜成纤维细胞分为阴性对照组和生物素标记的miR-708-5p过表达组,分别转染生物素标记的miR-708-5p模拟物阴性对照物和生物素标记的miR-708-5p模拟物; 48 h后,采用裂解液裂解细胞,加入链霉亲和素包被的磁珠孵育过夜; 收集各组磁珠检测circNOLC1水平。结果:①抑制circNOLC1表达对RA滑膜成纤维细胞影响的分析结果。circNOLC1抑制组RA滑膜成纤维细胞circNOLC1相对表达量、细胞活性、划痕愈合率、神经钙黏蛋白相对表达量均低于阴性对照组[1.00±0.00,0.35±0.03,t=37.528,P=0.000; 0.85±0.06,0.44±0.04,t=9.848,P=0.000;(65.48±5.87)%,(22.86±2.09)%,t=11.847,P=0.000; 0.64±0.04,0.22±0.02,t=16.267,P=0.000],细胞克隆数、侵袭细胞数均少于阴性对照组[(107.62±10.88)个,(42.69±4.39)个,t=9.647,P=0.000;(89.83±7.45)个,(38.08±3.45)个,t=10.918,P=0.000],上皮钙黏蛋白相对表达量高于阴性对照组(0.32±0.03,0.75±0.05,t=12.773,P=0.000)。②过表达miR-708-5p对RA滑膜成纤维细胞影响的分析结果。miR-708-5p过表达组RA滑膜成纤维细胞miR-708-5p相对表达量高于阴性对照组(1.00±0.00,2.91±0.21,t=15.753,P=0.000),细胞活性、划痕愈合率、神经钙黏蛋白相对表达量均低于阴性对照组[0.87±0.07,0.51±0.04,t=7.734,P=0.000;(69.89±6.17)%,(32.01±3.33)%,t=9.358,P=0.000; 0.65±0.04,0.28±0.02,t=8.036,P=0.000],细胞克隆数、侵袭细胞数均少于阴性对照组[(104.41±11.11)个,(51.37±5.12)个,t=7.510,P=0.000;(87.99±6.76)个,(49.58±4.78)个,t=11.288,P=0.000],上皮钙黏蛋白相对表达量高于阴性对照组(0.31±0.03,0.69±0.05,t=14.330,P=0.000)。③抑制circNOLC1和miR-708-5p表达对RA滑膜成纤维细胞影响的分析结果。circNOLC1和miR-708-5p联合抑制组RA滑膜成纤维细胞miR-708-5p相对表达量低于阴性对照组(1.00±0.00,0.29±0.03,t=40.992,P=0.000),细胞活性、划痕愈合率、神经钙黏蛋白相对表达量均高于阴性对照组(0.43±0.04,0.78±0.06,t=8.407,P=0.000;(21.07±2.29)%,(56.73±5.54)%,t=10.303,P=0.000; 0.21±0.02,0.56±0.05,t=9.881,P=0.000),细胞克隆数、侵袭细胞数均多于阴性对照组[(43.78±4.07)个,(89.06±7.67)个,t=9.032,P=0.000;(37.31±3.81)个,(75.81±5.57)个,t=9.468,P=0.000],上皮钙黏蛋白相对表达量低于阴性对照组(0.76±0.05,0.41±0.04,t=11.257,P=0.000)。④miR-708-5p与circNOLC1预测靶位点结合的验证结果。miR-708-5p过表达组野生型亚组RA滑膜成纤维细胞的相对荧光素酶活性低于阴性对照组野生型亚组(0.98±0.05,0.43±0.04,t=25.769,P=0.000); miR-708-5p过表达组突变型亚组相对荧光素酶活性高于miR-708-5p过表达组野生型亚组(0.43±0.04,0.99±0.07,t=12.031,P=0.000),且与阴性对照组突变型亚组的差异无统计学意义(1.00±0.07,0.99±0.07,t=0.303,P=0.766)。⑤circNOLC1与miR-708-5p在Ago2复合物中共富集的验证结果。抗Ago2抗体组RA滑膜成纤维细胞中circNOLC1、miR-708-5p水平均高于抗IgG抗体组(1.00±0.02,16.78±2.15,t=22.018,P=0.000; 1.00±0.03,11.56±2.63,t=12.045,P=0.000)。⑥circNOLC1与miR-708-5p靶向物理结合的验证结果。生物素标记的miR-708-5p过表达组RA滑膜成纤维细胞中circNOLC1水平高于阴性对照组(8.97±1.12,1.00±0.04,t=21.335,P=0.000)。结论:circNOLC1能够通过靶向吸附miR-708-5p影响RA滑膜成纤维细胞的活性及其增殖、迁移和侵袭能力。
Abstract:
Objective:To investigate the effects of circular RNA NOLC1(circNOLC1)and miR-708-5p on rheumatoid arthritis(RA)synovial fibroblasts and their mechanisms of action.Methods:①Method for obtaining RA synovial fibroblasts.Synovial tissues from patients with late-stage RA were collected to isolate and culture RA synovial fibroblasts.②Method for analyzing the effect of inhibiting circNOLC1 expression on RA synovial fibroblasts.RA synovial fibroblasts were divided into a negative control group and a circNOLC1 inhibition group, transfected with non-targeting small interfering RNA(siRNA)and circNOLC1-targeting siRNA, respectively; after 48-hour culture, the circNOLC1 expression level, cell viability, cell proliferation ability(number of cell clones), cell migration ability(scratch healing rate), cell invasion ability(number of invading cells), and expression levels of E-cadherin and N-cadherin were detected in each group.③Method for analyzing the effect of overexpressing miR-708-5p on RA synovial fibroblasts.RA synovial fibroblasts were divided into a negative control group and a miR-708-5p overexpression group, transfected with miR-708-5p mimic negative control and miR-708-5p mimic, respectively; after 48-hour culture, the miR-708-5p expression level, cell viability, cell proliferation ability(number of cell clones), cell migration ability(scratch healing rate), cell invasion ability(number of invading cells), and expression levels of E-cadherin and N-cadherin were detected in each group.④Method for analyzing the effect of inhibiting circNOLC1 and miR-708-5p expression on RA synovial fibroblasts.RA synovial fibroblasts were divided into a negative control group and a combined circNOLC1 and miR-708-5p inhibition group; the negative control group was transfected with circNOLC1-targeting siRNA and miR-708-5p inhibitor negative control, while the combined inhibition group was transfected with circNOLC1-targeting siRNA and miR-708-5p inhibitor; after 48-hour culture, various indicators of cells in each group were detected(same as in③).⑤Method for verifying the binding of miR-708-5p to the predicted target site of circNOLC1.RA synovial fibroblasts were divided into a negative control group and a miR-708-5p overexpression group, with each group further divided into a wild-type subgroup and a mutant subgroup.The wild-type subgroup of the negative control group was transfected with miR-708-5p mimic negative control and wild-type circNOLC1 psiCHECK-2 recombinant vector, and the mutant subgroup was transfected with miR-708-5p mimic negative control and mutant circNOLC1 psiCHECK-2 recombinant vector; the wild-type subgroup of the miR-708-5p overexpression group was transfected with miR-708-5p mimic and wild-type circNOLC1 psiCHECK-2 recombinant vector, and the mutant subgroup was transfected with miR-708-5p mimic and mutant circNOLC1 psiCHECK-2 recombinant vector.After 48-hour culture, the relative luciferase activity of RA synovial fibroblasts in each group was detected.⑥Method for verifying the co-enrichment of circNOLC1 and miR-708-5p in the Ago2 complex.RA synovial fibroblasts were divided into an anti-immunoglobulin G(IgG)antibody group and an anti-Ago2 antibody group; after cell lysis, magnetic beads coated with anti-IgG antibody and magnetic beads coated with anti-Ago2 antibody were added to the cell lysates of the anti-IgG antibody group and the anti-Ago2 antibody group, respectively, for incubation, and the beads were collected to detect circNOLC1 and miR-708-5p levels.⑦Method for verifying the targeted physical binding of circNOLC1 to miR-708-5p.RA synovial fibroblasts were divided into a negative control group and a biotin-labeled miR-708-5p overexpression group, transfected with biotin-labeled miR-708-5p mimic negative control and biotin-labeled miR-708-5p mimic, respectively; after 48 hours, cells were lysed using lysis buffer, and streptavidin-coated magnetic beads were added for overnight incubation; the magnetic beads from each group were collected to detect circNOLC1 levels.Results:①Analysis results of the effect of inhibiting circNOLC1 expression on RA synovial fibroblasts.The relative expression level of circNOLC1, cell viability, scratch healing rate, and relative expression level of N-cadherin in RA synovial fibroblasts in the circNOLC1 inhibition group were all lower than those in the negative control group(1.00±0.00 vs 0.35±0.03, t=37.528, P=0.000; 0.85±0.06 vs 0.44±0.04, t=9.848, P=0.000; 65.48±5.87 vs 22.86±2.09%, t=11.847, P=0.000; 0.64±0.04 vs 0.22±0.02, t=16.267, P=0.000), the number of cell clones and invading cells were both less than those in the negative control group(107.62±10.88 vs 42.69±4.39 cells, t=9.647, P=0.000; 89.83±7.45 vs 38.08±3.45 cells, t=10.918, P=0.000), and the relative expression level of E-cadherin was higher than that in the negative control group(0.32±0.03 vs 0.75±0.05, t=12.773, P=0.000).②Analysis results of the effect of overexpressing miR-708-5p on RA synovial fibroblasts.The relative expression level of miR-708-5p in RA synovial fibroblasts in the miR-708-5p overexpression group was higher than that in the negative control group(1.00±0.00 vs 2.91±0.21, t=15.753, P=0.000), while cell viability, scratch healing rate, and relative expression level of N-cadherin were all lower than those in the negative control group(0.87±0.07 vs 0.51±0.04, t=7.734, P=0.000; 69.89±6.17 vs 32.01±3.33%, t=9.358, P=0.000; 0.65±0.04 vs 0.28±0.02, t=8.036, P=0.000), the number of cell clones and invading cells were both less than those in the negative control group(104.41±11.11 vs 51.37±5.12 cells, t=7.510, P=0.000; 87.99±6.76 vs 49.58±4.78 cells, t=11.288, P=0.000), and the relative expression level of E-cadherin was higher than that in the negative control group(0.31±0.03 vs 0.69±0.05, t=14.330, P=0.000).③Analysis results of the effect of inhibiting circNOLC1 and miR-708-5p expression on RA synovial fibroblasts.The relative expression level of miR-708-5p in RA synovial fibroblasts in the combined circNOLC1 and miR-708-5p inhibition group was lower than that in the negative control group(1.00±0.00 vs 0.29±0.03, t=40.992, P=0.000), cell viability, scratch healing rate, and relative expression level of N-cadherin were all higher than those in the negative control group(0.43±0.04 vs 0.78±0.06, t=8.407, P=0.000; 21.07±2.29 vs 56.73±5.54%, t=10.303, P=0.000; 0.21±0.02 vs 0.56±0.05, t=9.881, P=0.000), the number of cell clones and invading cells were both more than those in the negative control group(43.78±4.07 vs 89.06±7.67 cells, t=9.032, P=0.000; 37.31±3.81 vs 75.81±5.57 cells, t=9.468, P=0.000), and the relative expression level of E-cadherin was lower than that in the negative control group(0.76±0.05 vs 0.41±0.04, t=11.257, P=0.000).④Verification results of the binding of miR-708-5p to the predicted target site of circNOLC1.The relative luciferase activity of RA synovial fibroblasts in the wild-type subgroup of the miR-708-5p overexpression group was lower than that in the wild-type subgroup of the negative control group(0.98±0.05 vs 0.43±0.04, t=25.769, P=0.000); the relative luciferase activity in the mutant subgroup of the miR-708-5p overexpression group was higher than that in the wild-type subgroup of the miR-708-5p overexpression group(0.43±0.04 vs 0.99±0.07, t=12.031, P=0.000), and the difference compared with the mutant subgroup of the negative control group was not statistically significant(1.00±0.07 vs 0.99±0.07, t=0.303, P=0.766).⑤Verification results of the co-enrichment of circNOLC1 and miR-708-5p in the Ago2 complex.The levels of circNOLC1 and miR-708-5p in RA synovial fibroblasts in the anti-Ago2 antibody group were both higher than those in the anti-IgG antibody group(1.00±0.02 vs 16.78±2.15, t=22.018, P=0.000; 1.00±0.03 vs 11.56±2.63, t=12.045, P=0.000).⑥Verification results of the targeted physical binding of circNOLC1 to miR-708-5p.The level of circNOLC1 in RA synovial fibroblasts in the biotin-labeled miR-708-5p overexpression group was higher than that in the negative control group(8.97±1.12 vs 1.00±0.04, t=21.335, P=0.000).Conclusion:The circNOLC1 can affect the viability, proliferation, migration and invasion abilities of RA synovial fibroblasts by targeting and adsorbing miR-708-5p.

参考文献/References:

[1] 丁娟,莫基浩.胰岛素样生长因子Ⅱ及胰岛素样生长因子结合蛋白-6血清水平与类风湿关节炎疾病活动度的关系研究[J].中医正骨,2023,35(11):10-13.
[2] 刘国印,吕德珍,陈建民,等.细胞内外GRP78/Bip在类风湿性关节炎病情活动和病程进展中的表达及意义[J].医学研究与战创伤救治,2025,38(3):245-252.
[3] 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.
[4] CHEN S,WU W,LI Q H,et al.Circ-NOLC1 promotes epithelial ovarian cancer tumorigenesis and progression by binding ESRP1 and modulating CDK1 and RhoA expression[J].Cell Death Discov,2021,7(1):22-35.
[5] CHEN W,CEN S,ZHOU X,et al.Circular RNA CircNOLC1,upregulated by NF-kappaB,promotes the progression of prostate cancer via miR-647/PAQR4 axis[J].Front Cell Dev Biol,2021,8:624764.
[6] WU X,TAN Y,TANG X.Long noncoding RNA MALAT1 promotes laryngocarcinoma development by targeting miR-708-5p/BRD4 axis to regulate YAP1-mediated epithelial-mesenchymal transition[J].Biomed Res Int,2022,2022:8093949.
[7] WU X,CUI F,CHEN Y,et al.Long non-coding RNA LOXL1-AS1 enhances colorectal cancer proliferation,migration and invasion through miR-708-5p/CD44-EGFR axis[J].Onco Targets Ther,2020,13:7615-7627.
[8] BI X,GUO X H,MO B Y,et al.LncRNA PICSAR promotes cell proliferation,migration and invasion of fibroblast-like synoviocytes by sponging miRNA-4701-5p in rheumatoid arthritis[J].EBioMedicine,2019,50:408-420.
[9] CAI Y,LIANG R,XIAO S,et al.Circ_0088194 promotes the invasion and migration of rheumatoid arthritis fibroblast-like synoviocytes via the miR-766-3p/MMP2 axis[J].Front Immunol,2021,12:628654.
[10] QU W,JIANG L,HOU G.Circ-AFF2/miR-650/CNP axis promotes proliferation,inflammatory response,migration,and invasion of rheumatoid arthritis synovial fibroblasts[J].J Orthop Surg Res,2021,16(1):165-176.
[11] 李志婷,姜刚刚,田杰祥,等.滑膜成纤维细胞焦亡在类风湿关节炎发病机制中的作用及中医药对其干预探讨[J].风湿病与关节炎,2023,12(4):37-41.
[12] 田晓静,薛宏峰,蒋辉,等.hsa_circ_0044235对类风湿关节炎滑膜成纤维细胞增殖和迁移的影响及机制[J].中国免疫学杂志,2022,38(22):2712-2717.
[13] 崔家康,高青杰,马俊福,等.circ_0005276靶向miR-557调控类风湿关节炎滑膜成纤维细胞的增殖、迁移和侵袭[J].实用医学杂志,2023,39(2):186-191.
[14] 李舒,万磊,刘健,等.circCBLB抑制类风湿性关节炎成纤维细胞样滑膜细胞增殖促进细胞凋亡并增加抗炎细胞因子水平[J].细胞与分子免疫学杂志,2024,40(2):106-113.
[15] CAI Y,QIU R,HUANG Q,et al.Circ_0088200 acts as a sponge for miR-127-5p to promote the migration and invasion of rheumatoid arthritis fibroblast-like synoviocytes[J].Rheumatol Immunol Res,2025,6(1):7-20.
[16] ZHAO P,MA G,MA L.Circ_0000479 promotes proliferation,invasion,migration and inflammation and inhibits apo-ptosis of rheumatoid arthritis fibroblast-like synoviocytes via miR-766/FKBP5 axis[J].J Orthop Surg Res,2023,18(1):220.
[17] LU J Z,YANG J,ZHOU S T,et al.Circ_0002984 promotes proliferation,migration and inflammatory cytokine secretion and inhibits apoptosis of rheumatoid arthritis fibroblast-like synoviocytes by inducing PCSK6 through miR-543[J].J Orthop Surg Res,2023,18(1):335.
[18] 范文强,马玲,吴洁,等.miR-708-5p对类风湿关节炎滑膜成纤维细胞凋亡、炎症因子分泌和TLR4/NF-κB信号通路的影响[J].郑州大学学报(医学版),2020,55(5):705-710.
[19] 王亚男,李艳,武文印,等.蒲公英提取物对类风湿性关节炎成纤维样滑膜细胞凋亡及炎症因子的影响[J].中国中医骨伤科杂志,2023,31(4):9-14.
[20] WU J,FAN W,MA L,et al.miR-708-5p promotes fibroblast-like synoviocytes'cell apoptosis and ameliorates rheumatoid arthritis by the inhibition of Wnt3a/β-catenin pathway[J].Drug Des Devel Ther,2018,12:3439-3447.
[21] 郑宏,曾振华,唐建生,等.circ-RAD23B通过miR-708-5p/CPNE1轴调控膀胱癌细胞增殖、细胞周期、凋亡的机制[J].中国老年学杂志,2022,42(17):4314-4320.
[22] BAULINA N M,KISELEV I S,CHUMAKOVA O S,et al.Circular RNAs:biogenesis,functions,and role in myocardial hypertrophy[J].Biochemistry(Mosc),2024,89(Suppl 1):S1-S13.
[23] 郭慧葛,孙四玉,林飞,等.circRNA/miRNA/mRNA的生物学功能及其对动脉粥样硬化的影响[J].中国动脉硬化杂志,2023,31(1):80-87.
[24] LIU X,SHEN X,ZHANG J.Long non-coding RNA LINC00514 promotes the proliferation and invasion through the miR-708-5p/HOXB3 axis in cervical squamous cell carcinoma[J].Environ Toxicol,2022,37(1):161-170.
[25] ZHU S,YANG Z,ZHANG Z,et al.HOXB3 drives WNT-activation associated progression in castration-resistant prostate cancer[J].Cell Death Dis,2023,14(3):215.

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　QI Xinyu,XIANG Lili,XIONG Hui,et al.A dose-effect relationship study of gouty arthritis chicken model built by high-protein diet[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2015,27(02):1.
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备注/Memo

备注/Memo:
通信作者:杨雯娣 E-mail:qbz986@163.com
(收稿日期:2024-01-26 本文编辑:吕宁)
更新日期/Last Update: 2026-02-20