AUTHOR=You Yi , Zhao Xingwang , Wu Yaguang , Mao Jiangming , Ge Lan , Guo Junkai , Zhao Chenglei , Chen Dong , Song Zhiqiang 

TITLE=Integrated Transcriptome Profiling Revealed That Elevated Long Non-Coding RNA-AC007278.2 Expression Repressed CCR7 Transcription in Systemic Lupus Erythematosus

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.615859

DOI=10.3389/fimmu.2021.615859

ISSN=1664-3224

ABSTRACT=<sec><title>Purpose</title><p>Systemic lupus erythematosus (SLE) is a serious autoimmune disease. Its molecular pathogenesis, especially the long non-coding RNA (lncRNA) function, remains unclear. We want to investigate the lncRNA dysregulation profile and their molecular mechanisms in SLE.</p></sec><sec><title>Methods</title><p>In this study, we analyzed the transcriptome profiles (RNA-seq) of peripheral blood mononuclear cells (PBMCs) from SLE patients and two published transcriptome datasets to explore lncRNA profiles. The differentially expressed lncRNAs were confirmed by quantitative real-time PCR in another set of female patients. We constructed the lncRNA-mRNA regulatory networks by performing weighted gene co-expression network analysis (WGCNA). Dysregulated lncRNA AC007278.2 was repressed by short hairpin RNA (shRNA) in Jurkat cells. Dual-luciferase reporter gene assay was performed to investigate the regulatory mechanism of AC007278.2 on target gene CCR7.</p></sec><sec><title>Results</title><p>We observed dominant up-regulation of transcripts, including mRNAs and lncRNAs, in SLE patients. By WGCNA method, we identified three modules that were highly related to SLE. We then focused on one lncRNA, <italic>AC007278.2</italic>, with a T-helper 1 lineage-specific expression pattern. We observed consistently higher <italic>AC007278.2</italic> expression in SLE patients. Co-expression network revealed that <italic>AC007278.2</italic> participated in the innate immune response and inflammatory bowel disease pathways. By knocking down <italic>AC007278.2</italic> expression, we found that <italic>AC007278.2</italic> could regulate the expression of inflammatory and cytokine stimulus response-related genes, including <italic>CCR7</italic>, <italic>AZU1</italic>, and <italic>TNIP3</italic>. <italic>AC007278.2</italic> inhibits the functional <italic>CCR7</italic> promoter to repress its transcription, thereby regulating autoimmunity and follicular T-helper cell differentiation.</p></sec><sec><title>Conclusion</title><p>In summary, our study indicated the important regulatory role of lncRNAs in SLE. <italic>AC007278.2</italic> may be treated as a novel biomarker for SLE diagnosis and treatment.</p></sec>