JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE) ›› 2020, Vol. 40 ›› Issue (8): 1030-1035.doi: 10.3969/j.issn.1674-8115.2020.08.005

• Original article (Basic research) • Previous Articles     Next Articles

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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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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