Xu Donghua, Jiang Ye, Yang Lu, Hou Xixing, Wang Jihong, Gu Weijun, Wang Xiaodong, Liu Lanyu, Zhang Juan, Lu Hongying
Department of Rheumatology and Immunology, The Affiliated Hospital of Weifang Medical University, Weifang 261000, China.
Clinical Medicine College of Weifang Medical University, Weifang 261000, China.
Oncotarget. 2017 Aug 8;8(56):95280-95292. doi: 10.18632/oncotarget.20036. eCollection 2017 Nov 10.
The modifying effects of long noncoding RNAs (lncRNAs) in rheumatoid arthritis (RA) recently have drawn much attention; however, the underlying mechanisms remain largely unknown. Herein, we aim to investigate the expression profile of lncRNAs in RA and identify promising targets for RA diagnosis and treatment. Microarray screening and real-time PCR of lncRNAs were performed by use of serum samples from 3 RA patients and 3 healthy controls. Significantly differentially expressed lncRNAs were verified in serum samples from 43 RA patients and 40 healthy controls by real-time PCR. We found that there were 73 up-regulated and 61 down-regulated lncRNAs as well as 128 up-regulated and 37 down-regulated mRNAs in serum samples of RA patients. Validation in RA clinical samples indicated 5 of these lncRNAs were significantly up-regulated including RNA143598, RNA143596, HIX0032090, IGHCgamma1, and XLOC_002730. Significant association was observed between these lncRNAs and the disease course, erythrocyte sedimentation rate (ESR), rheumatoid factor (RF) as well as anti-cyclic citrullinated peptide (anti-CCP) antibody. Additionally, 55 of the differentially expressed mRNAs were associated with 41 lncRNAs and were involved in signaling pathways of toll like receptors (TLRs), nuclear factor-kappa B (NF-κB), and cytokine, especially the IRF3/IRF7 mediated signaling transduction. Our study firstly shows the specific profile of lncRNAs in the serum of RA patients and potential signaling pathways involved in RA pathogenesis, which may provide novel targets for the diagnosis and treatment of patients with RA.
长链非编码RNA（lncRNAs）在类风湿关节炎（RA）中的调节作用近来备受关注；然而，其潜在机制仍 largely未知。在此，我们旨在研究RA中lncRNAs的表达谱，并确定RA诊断和治疗的有前景靶点。利用3例RA患者和3例健康对照的血清样本进行lncRNAs的微阵列筛选和实时PCR。通过实时PCR在43例RA患者和40例健康对照的血清样本中验证显著差异表达的lncRNAs。我们发现RA患者血清样本中有73个lncRNAs上调、61个lncRNAs下调，以及128个mRNA上调、37个mRNA下调。在RA临床样本中的验证表明这些lncRNAs中有5个显著上调，包括RNA143598、RNA143596、HIX0032090、IGHCgamma1和XLOC_002730。观察到这些lncRNAs与病程、红细胞沉降率（ESR）、类风湿因子（RF）以及抗环瓜氨酸肽（抗CCP）抗体之间存在显著关联。此外，55个差异表达的mRNA与41个lncRNAs相关，并参与Toll样受体（TLRs）、核因子-κB（NF-κB）和细胞因子的信号通路，尤其是IRF3/IRF7介导的信号转导。我们的研究首次展示了RA患者血清中lncRNAs的特定谱以及RA发病机制中涉及的潜在信号通路，这可能为RA患者的诊断和治疗提供新的靶点。
