A novel long noncoding RNA ENST00000597482 serves as a potential biomarker for disease activity and diagnosis of systemic lupus erythematosus

Author:

Wang Cuicui1,Yuan Shiwen1ORCID,Zeng Yanting1,Li Weinian1,Ye Jinghua1,Li Fangfei1ORCID,He Zhixiang1,Chen Yi1,Lin Xiaojun1,Liang Liuqin2,Xu Hanshi2,Cai Xiaoyan1ORCID

Affiliation:

1. Department of Rheumatology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, China

2. Department of Rheumatology and Immunology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China

Abstract

Objectives Emerging evidence indicate that long noncoding RNAs (lncRNAs) may play an important role in the pathogenesis of systemic lupus erythematosus (SLE) however, the contribution of lncRNAs to SLE remains largely unclear. Our study aimed to explore the lncRNA expression profiles in peripheral blood mononuclear cells (PBMCs) from SLE patients. Methods LncRNA sequencing was used to detect differentially expressed genes in PBMCs from 5 SLE-MIX samples and 3 healthy controls (HC)-MIX samples, and the expression of selected lncRNAs was further verified by real-time quantitative polymerase chain reaction (RT‒qPCR). The correlation of lncRNA expression with laboratory indicators as well the SLE disease activity index 2000 (SLEDAI‒2K) score from 72 SLE patients was assessed by Spearman’s test. The association between lncRNA ENST00000597482 and organ involvement in SLE patients was determined by the Mann‒Whitney U test. Moreover, lymphocyte subsets in peripheral blood from SLE patients were measured by flow cytometry. In addition, the diagnostic value of lncRNAs in predicting SLE was evaluated by receiver operating characteristic (ROC) curve analysis. Results The lncRNA expression profiles demonstrated 218 differentially expressed lncRNAs, including 121 upregulated genes and 97 downregulated genes, in PBMCs from SLE patients compared to HCs. Among the 10 candidate genes selected, only lncRNA ENST00000597482, which was lower in SLE PBMCs than in HCs, was consistent with the sequencing results. LncRNA ENST00000597482 expression was negatively correlated with SLEDAI-2K score and the titres of ANA antibodies and anti-double-stranded DNA (anti-dsDNA) antibodies. Of note, SLE patients with lower expression of lncRNA ENST00000597482 were prone to develop organ involvement. Furthermore, lncRNA ENST00000597482 exhibited potential diagnostic value in differentiating SLE patients from HCs. Conclusions LncRNA ENST00000597482 expression was lower in PBMCs from SLE patients than HCs and was negatively correlated with the SLEDAI-2K score and autoantibody titres. In addition, lncRNA ENST00000597482 could act as a novel biomarker for disease activity and diagnosis of SLE.

Funder

Ministry of Science and Technology of the People’s Republic of China > National Natural Science Foundation of China >

Natural Science Foundation of Guangdong Province

Guangzhou Municipal Science and Technology Bureau

Publisher

SAGE Publications

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