Identification of Long Noncoding RNA RP11-2B6.2 As a Positive Regulator through Type I Interferon Pathway in Lupus Nephritis

Yuanjia Tang¹, Zhuojun Liao¹, Zhixin Xue¹, Lingling Wu¹ and Nan Shen^1,2,3,4, ¹Shanghai Institute of Rheumatology,Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, ²Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, ³Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) & Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China, ⁴Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, Shanghai, China

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: SLE and interferons

Session Information

Date: Monday, November 6, 2017

Session Title: Systemic Lupus Erythematosus – Human Etiology and Pathogenesis Poster I

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose:

Long noncoding RNAs (lncRNAs) have recently been identified to be tightly linked to diverse human diseases. Systemic lupus erythematosus (SLE) is a common autoimmune disease. Renal involvement is the most frequent and serious complication. Type I interferon (I IFN) and a group of inflammatory cytokines induced by type I IFN in human renal mesangial cells(HRMCs) play a vital role in lupus nephritis(LN). In this study we screened and investigated the contribution of the lncRNA RP11-2B6.2 to the pathogenesis of LN involved in the abnormal activation of type I IFN pathway.

Methods:

The high throughput RNA-seq data from kidney biopsies of LN patients and controls was applied to screen for candidate lncRNA and confirm its relationship with clinical data. Rapid amplification of cDNA ends (RACE) was adopted to identify the full length and exact sequences of lncRNA. In situ hybridization was adopted to identify the lncRNA location of cell nucleus and cytoplasm. Quantitative real-time polymerase chain reaction(RT-qPCR) and western blotting was used to detect the RNA and protein expression of lncRNA and individual genes relevant to type I IFN pathway respectively. Dual-luciferace reporter assay was used to detect the promoter transcriptional activity of genes.

Results:

The expression of lncRNA RP11-2B6.2 was significantly increased in the kidney tissues from LN patients compared with those from healthy controls, and positively correlated with the degree of disease activity and renal injury. Additionally, the expression of LncRNA RP11-2B6.2 can be stimulated by type I IFN. Silencing RP11-2B6.2 significantly reduced the expression of a group of interferon-stimulating genes(ISGs) including IFIT1, OAS1, etc., Furthermore, lncRNA RP11-2B6.2 affected the expression of IFN alpha and beta receptor subunit 1 (IFNAR1) and its promoter transcriptional activity, phosphorylation of Jak1 and Stat1, and the luciferase activity induced by interferon stimulated response element(ISRE).

Conclusion:

Long noncoding RNA RP11-2B6.2 is a positive regulator of the type I IFN signaling pathway in LN. LncRNA RP11-2B6.2 may contribute to the pathogenesis of LN and provide a potentially therapeutic target.

Disclosure: Y. Tang, None; Z. Liao, None; Z. Xue, None; L. Wu, None; N. Shen, None.

To cite this abstract in AMA style:

Tang Y, Liao Z, Xue Z, Wu L, Shen N. Identification of Long Noncoding RNA RP11-2B6.2 As a Positive Regulator through Type I Interferon Pathway in Lupus Nephritis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/identification-of-long-noncoding-rna-rp11-2b6-2-as-a-positive-regulator-through-type-i-interferon-pathway-in-lupus-nephritis/. Accessed August 11, 2020.

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