临床与病理杂志2024，Vol.44Issue(3)：354-362,9.DOI:10.11817/j.issn.2095-6959.2024.230186
IGF2BP1调控lncRNA NEAT1在类风湿关节炎中的作用
Role of IGF2BP1 in regulating lncRNA NEAT1 in rheumatoid arthritis
摘要
Abstract
Objective:Rheumatoid arthritis(RA)is a prevalent systemic autoimmune disease that can lead to joint deformity and dysfunction.This study aims to explore the expression level of insulin-like growth factor 2 mRNA binding protein 1(IGF2BP1)in RA,its impact on the stability of long noncoding RNA(lncRNA)nuclear paraspeckle assembly transcript 1(NEAT1),and its mechanism in RA pathogenesis. Methods:RA datasets were obtained from the Gene Expression Omnibus(GEO)database and categorized into a normal control group and a RA group.R software was used to analyze the expression of N6-methyladenosine(m6A)-related methyltransferases and differential analysis were performed.The correlation between differentially expressed m6A methyltransferases and lncRNA NEAT1 was examined.Proteins predicted to bind with lncRNA NEAT1 were identified using the ENCORI online database,and key genes intersecting with m6A methyltransferases associated with lncRNA NEAT1 expression were identified.RNA pull-down assays were used to verify the binding of NEAT1 with key genes in RA synovial cells.Western blotting was used to verify the expression levels of key genes in normal and RA synovial cells.After transfecting IGF2BP1 small interfering RNA(siRNA)into RA synovial cells,the expression level of NEAT1 was detected by real-time RT-PCR. Results:Differential analysis showed that,compared to the normal control group,8 m6A-methyltransferase genes were differentially expressed in the RA group,with IGF2BP1 and methyltransferase 14,N6-adenosine-methyltransferase subunit(MEEEL14)showing correlation with lncRNA NEAT1.ENCORI prediction results indicated that 23 proteins could bind to lncRNA NEAT1.The intersection with NEAT1 co-expressed m6A methyltransferases identified IGF2BP1 as the NEAT1-related m6A methyltransferase.Western blotting revealed that IGF2BP1 protein expression was significantly elevated in the RA group compared to the normal group(P<0.05).RNA pull-down assays demonstrated that IGF2BP1 protein binds to NEAT1.Real-time RT-PCR results showed that knockdown of IGF2BP1 significantly reduced NEAT1 mRNA expression levels(P<0.01). Conclusion:IGF2BP1 may participate in RA pathogenesis by stabilizing lncRNA NEAT1 expression.Regulating IGF2BP1 levels could be a novel therapeutic approach for RA.关键词
类风湿关节炎/N6-甲基腺苷甲基化/长链非编码RNA核丰富转录本1/胰岛素样生长因子-2 mRNA结合蛋白1/生物信息学Key words
rheumatoid arthritis/m6A methylation/long noncoding RNA nuclear paraspeckle assembly transcript 1/insulin-like growth factor 2 mRNA binding protein 1/bioinformatics引用本文复制引用
肖剑伟,蔡旭,黄新民,洪易炜,颜真波,陈新鹏..IGF2BP1调控lncRNA NEAT1在类风湿关节炎中的作用[J].临床与病理杂志,2024,44(3):354-362,9.基金项目
广东省中医药管理局中医药科研项目(20221342),深圳市福田区卫生公益性科研项目(FTWS2021026,FTWS2021063,FTWS2021064,FTWS2022021).This work was supported by Chinese Medicine Research Project of Traditional Chinese Medicine Bureau Of Guangdong Province(20221342)and the Medical Science and Technology Research Fund in Futian District,Shenzhen(FTWS2021026,FTWS2021063,FTWS2021064,FTWS2022021),China. （20221342）
