Long noncoding RNA MALAT-1 is a novel inflammatory regulator in human systemic lupus erythematosus

被引:80
|
作者
Yang, Huaxia [1 ,2 ]
Liang, Naixin [3 ,4 ]
Wang, Min [1 ,2 ]
Fei, Yunyun [1 ,2 ]
Sun, Jian [4 ,5 ]
Li, Zhiyuan [4 ,5 ]
Xu, Yuan [3 ,4 ]
Guo, Chao [3 ,4 ]
Cao, Zhili [3 ,4 ]
Li, Shanqing [3 ,4 ]
Jiao, Yuchen [6 ]
机构
[1] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Rheumatol & Clin Immunol, Clin Immunol Ctr,Minist Educ,Key Lab, Beijing, Peoples R China
[2] Peking Union Med Coll, Beijing, Peoples R China
[3] Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Thorac Surg, Beijing, Peoples R China
[4] Chinese Acad Med Sci, Beijing, Peoples R China
[5] Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Pathol, Beijing, Peoples R China
[6] Chinese Acad Med Sci, Canc Hosp, Natl Key Lab Mol Oncol, Beijing, Peoples R China
关键词
MALAT-1; lncRNA; SLE; PBMC; IL-21; MESSENGER-RNA; EXPRESSION; NETWORKS;
D O I
10.18632/oncotarget.20490
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Despite growing evidence that Long noncoding RNAs (lncRNAs) can regulate gene expression and widely take part in autoimmune and inflammatory diseases, our knowledge of systemic lupus erythematosus (SLE)-related lincRNAs remains limited. In this study, we aimed to explore the contribution of the lncRNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) to the pathogenesis of SLE. PBMCs were obtained from SLE patients and healthy donors. The expression levels of MALAT-1 were measured by quantitative PCR. Small interfering RNA (siRNA) was then used to knock down the expression of MALAT1 in order to determine the role of MALAT1 in the expression levels of IL-21 and SIRT1 signaling pathway in primary monocytes of SLE patients. Here, we found MALAT-1 expression was abnormally increased in SLE patients and predominantly expressed in human monocytes. Additionally, silencing MALAT-1 significantly reduced the expression of IL-21 in primary monocytes of SLE patients. Furthermore, MALAT-1 exerts its detrimental effects by regulating SIRT1 signaling. Our results demonstrate that MALAT-1 is the key regulatory factor in the pathogenesis of SLE and provides potentially novel target for therapeutic intervention.
引用
收藏
页码:77400 / 77406
页数:7
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