上海交通大学学报（医学版）

上海交通大学学报(医学版) ›› 2020, Vol. 40 ›› Issue (08): 1030-1035.doi: 10.3969/j.issn.1674-8115.2020.08.005

• 论著·基础研究 • 上一篇    下一篇

长链非编码RNA AC073046.25在系统性红斑狼疮易感基因TET3表达调节中的作用

徐 宁，周 甜，侯国俊，沈 南，唐元家   

  1. 上海交通大学医学院附属仁济医院风湿病科，上海市风湿病学研究所，上海 200127
  • 出版日期:2020-08-28 发布日期:2020-08-28
  • 通讯作者: 唐元家，电子信箱：tangyuanjia028@163.com。
  • 作者简介:徐 宁（1993—），男，硕士生；电子信箱：sjtuxuning@foxmail.com。
  • 基金资助:
    国家自然科学基金（81871287，31630021，31930037）；上海交通大学医学院高水平地方高校创新团队（SSMU-ZDCX20180100）。

Role of long noncoding RNA AC073046.25 in regulation of systemic lupus erythematosus susceptibility gene TET3 expression

XU Ning, ZHOU Tian, HOU Guo-jun, SHEN Nan, TANG Yuan-jia   

  1. Shanghai Institute of Rheumatology, Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
  • Online:2020-08-28 Published:2020-08-28
  • Supported by:
    National Natural Science Foundation of China (81871287, 31630021, 31930037); Innovative Research Team of High-Level Local Universities in Shanghai (SSMU-ZDCX20180100).

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摘要： 目的·探究长链非编码RNA（long noncoding RNA，lncRNA）AC073046.25在单核细胞中对Tet 甲基胞嘧啶双加氧酶3（Tet methylcytosine dioxygenase 3，TET3）表达的调控作用，分析其作为系统性红斑狼疮（systemic lupus erythematosus，SLE）诊断的生物标志物的可行性。方法·通过表观遗传学修饰及胞浆胞核定位对AC073046.25的细胞特异性及功能进行预测。在U-937细胞中利用反义寡核苷酸（antisense oligonucleotide，ASO）对AC073046.25进行敲低（knock down），通过实时荧光定量PCR分析ASO敲低AC073046.25后对TET3表达水平的影响。收集健康志愿者（n=32）与SLE患者（n=46）的单核细胞，通过皮尔逊系数分析AC073046.25与TET3表达水平之间的相关性。将健康志愿者记为健康对照组，同时按系统性红斑狼疮疾病活动指数（systemic lupus erythematosus disease activity index，SLEDAI）评分标准将SLE患者分为疾病稳定组和疾病活跃组，采用非配对双侧student's t检验比较AC073046.25与TET3在健康对照组及不同疾病活动组间的差异。结果·表观遗传学数据及胞浆胞核定位实验提示，AC073046.25可能在单核细胞中参与TET3的表达调控。在U-937细胞中，ASO敲低AC073046.25后，TET3表达水平降低（ASO组均P=0.002）。相关性分析显示，原代单核细胞中AC073046.25与TET3的表达呈正相关（r=0.650，P=0.000）。非配对双侧student's t检验结果显示，分别与健康对照组和疾病稳定组相比，AC073046.25在疾病活跃组中的表达水平降低（P=0.002，P=0.000）。结论·在单核细胞中AC073046.25能够调控TET3的表达，在疾病活动度较高的SLE患者单核细胞中其表达水平显著降低；继而提示，AC073046.25可作为活跃性SLE的生物标志物辅助疾病活动性诊断。

关键词: 长链非编码RNA, Tet甲基胞嘧啶双加氧酶 3, 系统性红斑狼疮, 易感基因

Abstract:

Objective · To investigate the regulatory effect of long noncoding RNA (lncRNA) AC073046.25 on the expression of Tet methylcytosine dioxygenase 3 (TET3) in monocytes, and analyze the feasibility of AC073046.25 as a biomarker for the diagnosis of systemic lupus erythematosus (SLE). Methods · The cell specificity and function of AC073046.25 were predicted by epigenetic modification and cytoplasm/nuclear location experiment. In U-937 cells, antisense oligonucleotide (ASO) was used to knock down AC073046.25. The effect of ASO knockdown on TET3 expression was analyzed by quantitative real-time PCR. Monocytes from healthy volunteers (n=32) and SLE patients (n=46) were collected. The correlation between AC073046.25 and TET3 expression was analyzed by Pearson coefficient. Healthy volunteers were included in the healthy control group, and the SLE patients were divided into SLE-inactive group and SLE-active group according to the systemic lupus erythematosus disease activity index (SLEDAI). The differences of AC073046.25 and TET3 expression in healthy control group and different disease activity groups were compared by unpaired bilateral student's t test. Results · The epigenetic modification and cytoplasm/nuclear location experiment showed that AC073046.25 may be involved in the regulation of TET3 expression in monocytes. In U-937 cells, after ASO knocked down AC073046.25, TET3 expression level decreased (both P=0.002 in ASO groups). Correlation analysis showed that AC073046.25 expression was positively correlated with TET3 expression in primary monocytes (r=0.650, P=0.000). Unpaired bilateral student's t test showed that the expression level of AC073046.25 in the SLE-active group was lower than that in the healthy control group (P=0.002) and the SLE-inactive group (P=0.000). Conclusion · In monocytes, AC073046.25 can regulate the expression of TET3, and its expression is significantly decreased in monocytes derived from disease active SLE patients, which implicating that AC073046.25 can be thought as a biomarker for SLE disease activity diagnosis.

Key words: long noncoding RNA (lncRNA), Tet methylcytosine dioxygenase 3 (TET3), systemic lupus erythematosus (SLE), susceptibility gene

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