Identification of the Long Noncoding RNA NEAT1 As a Novel Inflammatory Regulator Acting through MAPK Pathway in Human Lupus

Yuanjia Tang¹, Feifei Zhang², Bo Qu³ and Nan Shen⁴, ¹Shanghai Institute of Rheumatology, Renji Hospital,Shanghai JiaoTong University School of Medicine, Shanghai, China, ²Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) & Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China, Shanghai, China, ³Shanghai Institute of Rheumatology,Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, ⁴The Center for Autoimmune Genomics and Etiology (CAGE),Cincinnati Children’s Hospital Medical Center,Cincinnati, Ohio, United States of America, Cincinnati, OH

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: systemic lupus erythematosus (SLE) and toll-like receptors

Session Information

Date: Monday, November 9, 2015

Title: Systemic Lupus Erythematosus - Human Etiology and Pathogenesis Poster II

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. This study was undertaken to investigate the contribution of the lncRNA NEAT1 which was identified to be involved in innate immune response to the pathogenesis of Systemic Lupus Erythematosus (SLE)

Methods: RT-PCR was used to compare NEAT1 expression between SLE patients and controls. Stimulation and transfection in THP-1 cells were conducted to determine the biologic function of NEAT1. Microarray and Western Blotting were performed to investigate in which pathway NEAT1 was involved. Correlation between NEAT1 expression and the disease activity of SLE patients was evaluated.

Results: NEAT1 expression was abnormally increased in the peripheral blood mononuclear cells (PBMCs) of SLE patients. We sorted the main three subsets of PBMCs (T cells, B cells, Monocytes), then compared the NEAT1 expression between SLE patients and healthy donors in these cell subsets in details and respectively. It was showed NEAT1 dominantly expressed in monocytes and was significantly up-regulated in monocytes of SLE patients compared with normal controls. Additionally, NEAT1 expression was induced by LPS via p38 activation in THP-1, the monocytic cell lines. We wondered whether or not NEAT1 would be involved in regulation of LPS-triggered induction of numerous inflammatory factors and found silencing NEAT1 significantly reduced the expression of a group of chemokines and cytokines, including IL-6, CXCL10, etc., which were induced by LPS continuously and in late stages. Furthermore, it was identified that NEAT1 selectively regulates LPS continuously-induced and late-response genes mainly through affecting the activation of the late MAPK pathway, especially the activation of JNK and ERK. Importantly, it was observed that in SLE patients, the overexpressed NEAT1 level correlates positively with the disease activity and NEAT1-regulated cytokines and chemokines.These indicate NEAT1 may be a potential contributor to the pathogenesis of lupus patients.

Conclusion: NEAT1 regulates a subset of LPS-induced inflammatory factors through affecting the activation of MAPK signaling pathway. The increased NEAT1 expression may be a potential contributor to the elevated production of a number of cytokines and chemokines in SLE patients. Our findings suggest lncRNA contributes to the pathogenesis of lupus and provides potential novel target for therapeutic intervention.

Disclosure: Y. Tang, None; F. Zhang, None; B. Qu, None; N. Shen, None.

To cite this abstract in AMA style:

Tang Y, Zhang F, Qu B, Shen N. Identification of the Long Noncoding RNA NEAT1 As a Novel Inflammatory Regulator Acting through MAPK Pathway in Human Lupus [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/identification-of-the-long-noncoding-rna-neat1-as-a-novel-inflammatory-regulator-acting-through-mapk-pathway-in-human-lupus/. Accessed .

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