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Front. Immunol. | doi: 10.3389/fimmu.2018.02967

Identification of Linc00513 as a Novel Interferon Signaling Pathway Regulatory LncRNA Containing Lupus-Associated genetic variants in the Promoter

Zhixin Xue1, Chaojie Cui1, Zhuojun Liao1, Shiwei Xia1, Pingjing Zhang1, Jialin Qin1, Qiang Guo1, Sheng Chen1, Zhihua Yin2, Zhizhong Ye1,  Yuanjia Tang1* and  Nan Shen1, 3, 4, 5*
  • 1Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, China
  • 2Shenzhen Futian Hospital for Rheumatic Diseases, China
  • 3Institute of Health Sciences, Shanghai Institutes for Biological Sciences (CAS), China
  • 4Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center, United States
  • 5Department of Pediatrics, University of Cincinnati College of Medicine, United States

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by augmented type I interferon signaling. High-throughput technologies have identified plenty of SLE susceptibility SNPs yet the exact roles of most of them are still unknown. Functional studies are principally focused on SNPs in the coding regions, with limited attention paid to the SNPs in noncoding regions. Long noncoding RNAs (lncRNAs) are important players in shaping the immune response and show relationship to autoimmune diseases. In order to reveal the role of SNPs located near SLE related lncRNAs, we performed a transcriptome profiling of SLE patients and identified linc00513 as a significantly over expressed lncRNA that contain functional SLE susceptibility loci in the promoter region. The risk-associated G allele of rs205764 and A allele of rs547311 enhanced linc00513 promoter activity and related to increased expression of linc00513 in SLE neutrophils. We also identified linc00513 to be a novel positive regulator of type I interferon pathway by promoting the phosphorylation of STAT1 and STAT2. Elevated linc00513 expression positively correlated with IFN score in neutrophils of SLE patients. Linc00513 expression was higher in disease active patients than those inactive ones. In conclusion, our data identify two functional promoter variants of linc00513 that contribute to increased level of linc00513 and confer susceptibility on SLE. The study provides new insights into the genetics of SLE and suggests lncRNAs can be novel biomarkers of SLE pathogenesis.

Keywords: Single-nucleotide polymorphism, long noncoding RNA, systemic lupus erythematosus, interferon, CRISPR-dCas9

Received: 16 Sep 2018; Accepted: 03 Dec 2018.

Edited by:

José C. Crispín, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Mexico

Reviewed by:

Carmelo Carmona-Rivera, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), United States
Iris K. Madera-Salcedo, Departamento de Inmunología y Reumatología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico  

Copyright: © 2018 Xue, Cui, Liao, Xia, Zhang, Qin, Guo, Chen, Yin, Ye, Tang and Shen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Yuanjia Tang, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, tangyuanjia028@163.com
Dr. Nan Shen, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, nanshensibs@gmail.com