Yang Huaxia, Liang Naixin, Wang Min, Fei Yunyun, Sun Jian, Li Zhiyuan, Xu Yuan, Guo Chao, Cao Zhili, Li Shanqing, Jiao Yuchen
Department of Rheumatology and Clinical Immunology, Clinical Immunology Center, The Ministry of Education Key Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Thoracic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Oncotarget. 2017 Aug 24;8(44):77400-77406. doi: 10.18632/oncotarget.20490. eCollection 2017 Sep 29.
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.
尽管越来越多的证据表明长链非编码RNA(lncRNAs)能够调控基因表达并广泛参与自身免疫性疾病和炎症性疾病,但我们对系统性红斑狼疮(SLE)相关的长链间充质RNA(lincRNAs)的了解仍然有限。在本研究中,我们旨在探究长链非编码RNA转移相关肺腺癌转录本1(MALAT1)在SLE发病机制中的作用。从SLE患者和健康供体获取外周血单个核细胞(PBMCs)。通过定量PCR检测MALAT-1的表达水平。然后使用小干扰RNA(siRNA)敲低MALAT1的表达,以确定MALAT1在SLE患者原代单核细胞中白细胞介素-21(IL-21)表达水平和沉默信息调节因子1(SIRT1)信号通路中的作用。在此,我们发现SLE患者中MALAT-1表达异常增加,且主要在人单核细胞中表达。此外,沉默MALAT-1可显著降低SLE患者原代单核细胞中IL-21的表达。此外,MALAT-1通过调节SIRT1信号发挥其有害作用。我们的结果表明,MALAT-1是SLE发病机制中的关键调节因子,并为治疗干预提供了潜在的新靶点。