POS0416 NOVEL LONG NON-CODING RNA EXPRESSION PROFILE OF PERIPHERAL BLOOD MONOUCLEAR CELL REVEALED POTENTIAL BIOMARKERS AND REGULATORY MECHANISM IN SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: Q. Cheng, M. Chen, X. Chen, X. Chen, H. Wu, Y. Du
Journal: Annals of the Rheumatic Diseases (2021)

Background: Systemic lupus erythematosus (SLE) is a complex and heterogeneous autoimmune disease, usually involving multiple systems of the whole body (1). A variety of factors can affect SLE, such as genetic, environmental, immunoregulatory, hormonal and epigenetic (2). Long non-coding RNA is a type of RNA greater than 200 nucleotides that does not encode proteins. With the development of research, lncRNA gradually becomes the key regulator of gene expression in the immune system (3). Studies have shown that several lncRNAs, such as NEAT1 and GAS5 are dysregulated in SLE and are involved in the pathogenesis of SLE (4,5). These results suggest that lncRNA can be used as a potential biomarker for disease diagnosis and treatment. However, our current understanding of SLE related lncRNAS is still limited. Objectives: The purpose of this study was to find new lncRNAs in peripheral blood monouclear cells of SLE patients by transcriptome sequencing and explore their potential as biomarkers and their correlation with clinical features. Methods: Transcriptome sequencing was used to screen differentially expressed lncRNAs (DELs) and mRNAs (DEMs). DAVID and WebGestalt were used to perform enrichment analysis. Cytoscape was used to constructed protein-protein network, co-expression network and competitive endogenous RNA network to reveal the regulatory mechanism of lncRNAs in transcriptome level. The expression of these selected lncRNAs in SLE patients and healthy controls were verified by qPCR. Results: A toal of 1737 DELs and 4078 DEMs were identified between 5 SLE patients and 5 healthy controls. Most of upregulated genes were enriched in defense and immune response, while downregulated genes were mainly enriched in SLE related pathways. Topology network analysis reveal the regulatory mechanism of lncRNAs in transcriptome level including directly acting on mRNA or indirectly affecting gene expression after acting on miRNA. Ten lncRNAs and eight genes was verified by qPCR in bigger samples including 77 SLE patients and 25 healthy controls. LncRNA NONHSAT101022.2 was significantly downregulated in SLE patients ( p=0.001 ) and the expression of NONHSAT101022.2 showed a significant negative correlation with SLE disease activity index (SLEDAI, r=-0.3592, p=0.0013 ). Conclusion: In this work, we identified a large number of mRNAs and novel lncRNAs by transcriptome sequence. The function and regulatory mechanism of these lncRNAs were analyzed by bioinformatics methods. LncRNA NONHSAT101022.2 is significantly downregulated in SLE patients and significantly related to the activity and severity of disease. Additionally, we put forward that NONHSAT101022.2 may enhance the signal transduction of β2-AR by cis-regulating its target gene, LMBRD2, which induces NK cells to produce high levels of IFN-γ, thereby exacerbating SLE. References: [1]Carter EE, Barr SG, Clarke AE. The global burden of SLE: prevalence, health disparities and socioeconomic impact. Nat Rev Rheumatol. 2016;12(10):605-20. [2]Han EC. Systemic lupus erythematosus. N Engl J Med. 2012;366(6):573-4; author reply. [3]Chen YG, Satpathy AT, Chang HY. Gene regulation in the immune system by long noncoding RNAs. Nat Immunol. 2017;18(9):962-72. [4]Zhang F, Wu L, Qian J, Qu B, Xia S, La T, et al. Identification of the long noncoding RNA NEAT1 as a novel inflammatory regulator acting through MAPK pathway in human lupus. Journal of autoimmunity. 2016;75:96-104. [5]Liu Q, Deng Y, Li C, Xie H, Liu Q, Ming S, et al. LncRNA GAS5 suppresses CD4(+) T cell activation by upregulating E4BP4 via inhibiting miR-92a-3p in systemic lupus erythematosus. Immunol Lett. 2020;227:41-7. Disclosure of Interests: None declared