Sourour Shady K, Aboelenein Heba R, Elemam Noha M, Abdelhamid Amira K, Salah Samia, Abdelaziz Ahmed I
Department of Pharmacology and Toxicology, German University in Cairo, Cairo, Egypt.
Sharjah Institute for Medical Research (SIMR), College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
Int J Rheum Dis. 2017 Sep;20(9):1237-1246. doi: 10.1111/1756-185X.13099. Epub 2017 May 19.
The activity of natural killer (NK) cells is known to be decreased in systemic lupus erythematosus (SLE) patients. Nevertheless, the exact contribution of NK cells in the pathogenesis of SLE is still inconclusive. MicroRNAs (miRNAs), are small noncoding RNA molecules that play a fundamental role in regulating NK cell function. The objective of this study was to investigate the expression of miRNAs that might potentially target an essential activating receptor, NKG2D in peripheral blood mononuclear cells (PBMCs) and NK cells of SLE patients.
In silico analysis revealed miR-27a* to potentially target NKG2D messenger RNA (mRNA), hence PBMCs and NK cells were isolated from blood samples of SLE patients and healthy controls. Next, the cells were transfected using mimics and antagomirs, after which miRNA/mRNA were quantified using real time quantitative reverse transcription polymerase chain reaction.
The results of this study showed that miR-27a* is overexpressed in the PBMCs and NK cells of SLE patients. In contrast, NKG2D was found to be downregulated in PBMCs and NK cells of SLE patients. Forcing the expression of miR-27a* in PBMCs and NK cells enhances the expression of NKG2D in SLE patients. Furthermore, the ligand of NKG2D, ULBP2, was found to be downregulated in the PBMCs of SLE patients.
The altered expression of the triad, miR-27a* as well as NKG2D and ULBP2, is thought to be characteristic for NK cells in SLE patients. Hence, the ability of miR-27a* to alter the expression of NKG2D may provide a new groundwork for understanding the role of miRNAs in NK cells of SLE patients.
已知系统性红斑狼疮（SLE）患者体内自然杀伤（NK）细胞的活性会降低。然而，NK细胞在SLE发病机制中的确切作用仍无定论。微小RNA（miRNA）是一类小的非编码RNA分子，在调节NK细胞功能中起重要作用。本研究的目的是调查可能潜在靶向一种重要激活受体NKG2D的miRNA在SLE患者外周血单个核细胞（PBMC）和NK细胞中的表达情况。
计算机分析显示miR-27a*可能靶向NKG2D信使核糖核酸（mRNA），因此从SLE患者和健康对照者的血液样本中分离出PBMC和NK细胞。接下来，使用模拟物和拮抗剂对细胞进行转染，之后使用实时定量逆转录聚合酶链反应对miRNA/mRNA进行定量。
本研究结果表明，miR-27a在SLE患者的PBMC和NK细胞中过表达。相反，发现NKG2D在SLE患者的PBMC和NK细胞中表达下调。在PBMC和NK细胞中强制表达miR-27a可增强SLE患者中NKG2D的表达。此外，发现NKG2D的配体ULBP2在SLE患者的PBMC中表达下调。
miR-27a以及NKG2D和ULBP2这三者表达的改变被认为是SLE患者NK细胞的特征。因此，miR-27a改变NKG2D表达的能力可能为理解miRNA在SLE患者NK细胞中的作用提供新的基础。
