河北医学2024，Vol.30Issue(9)：1434-1439,6.DOI:10.3969/j.issn.1006-6233.2024.09.04
LncRNA MALAT1通过募集EZH2介导系统性红斑狼疮相关抗炎基因表观遗传沉默
LncRNA MALAT1 Mediates Epigenetic Silencing of Systemic Lupus Erythematosus-Associated Anti-Inflammatory Genes through Recruitment of EZH2
摘要
Abstract
Objective:To explore the correlation of long non-coding RNA(LncRNA)MALAT1 and methyltransferase EZH2 with SLE-associated anti-inflammatory factors and the molecular regulatory mecha-nism.Methods:Peripheral blood mononuclear cells(PBMC)were extracted from healthy controls(n=10)and SLE patients(n=10),and mRNA levels of LncRNA MALAT1,EZH2,and anti-inflammatory factors PTEN,Ets-1,and FOXO1 were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).The correlation between LncRNA MALAT1,EZH2,and the expression of stress factors was verified respectively.After transfecting THP-1 cells with small interfering RNA(si-RNA),the expression of various anti-inflammatory factors was detected by RT-qPCR after LncRNA MALAT1 and EZH2 was knocked down,and the interaction between LncRNAMALAT1 and EZH2 was verified by RNA immunoprecipitation(RIP).After simultaneous knockdown of EZH2 and overexpression of LncRNAMALAT1,the 27th lysine(K27)trimethylation(me3)level of histone 3(H3)was detected by Western blot(western blot).Results:Compared with healthy controls,PBMC LncRNAMALAT1 and EZH2 in peripheral blood of SLE patients were significantly overexpressed(P<0.05),anti-inflammatory factors PTEN,Ets-1,and FOXO1 were signifi-cantly decreased(P<0.05),and LncRNA MALAT1 and EZH2 were significantly negatively correlated with the anti-inflammatory expressions.The expressions of various anti-inflammatory factors were significantly in-creased after LncRNA MALAT1 and EZH2 were knocked down respectively(P<0.05).The RIP result shows that LncRNA MALAT1 and EZH2 combine.After overexpression of LncRNA MALAT1,the expression of anti-inflammatory factors was significantly decreased.Still,the expression of anti-inflammatory factors was in-creased and H3K27me3 was decreased considerably when EZH2 was knocked down and LncRNA MALAT1 was overexpressed at the same time(P<0.05).Conclusion:The expression of LncRNA MALAT1 and EZH2 is significantly negatively correlated with the expression of SLE-associated anti-inflammatory factors,and the molecular mechanism is related to LncRNA MALAT1 regulating the expression of H3K27me3 by recruiting EZH2.关键词
甲基化转移酶/表观遗传学沉默/系统性红斑狼疮/抗炎因子Key words
Methyltransferase/Epigenetic silencing/Systemic lupus erythematosus/Anti-in-flammatory factor引用本文复制引用
高飞,谈园,张莲,罗立芳,罗雯,马乐,黎姣艳,黄敖..LncRNA MALAT1通过募集EZH2介导系统性红斑狼疮相关抗炎基因表观遗传沉默[J].河北医学,2024,30(9):1434-1439,6.基金项目
湖南省卫生健康委科研计划项目,(编号:202104120051) （编号:202104120051）
长沙市科学技术局项目,(编号:kdz2401039) （编号:kdz2401039）
