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

Systemic lupus erythematosus (SLE) is a serious autoimmune disease whose molecular pathogenesis is not well understood, especially the functions long noncoding RNAs (lncRNAs) in SLE development. In this study, we integrated the transcriptome profiles (RNA-seq) of peripheral blood mononuclear cells (PMBCs) from SLE patients and two published RNA-seq datasets to explore the expression profile of lncRNAs. Bioinformatics analysis of these data revealed the dominant up-regulation of transcripts in SLE patients, including mRNAs and lncRNAs. Functional enrichment analysis also revealed the highly correlation between the up-regulated transcripts and disease. We constructed the lncRNA-mRNA regulatory networks by performing WGCNA analysis and found three modules that were highly related with SLE. We then focused on one lncRNA, AC007278.2, coming from a cytokine receptor genes locus in Chr2, with Th1 lineage specific expression pattern in previous study. We found it was with consistent higher expression level in SLE patients. Co-expression network revealed AC007278.2 participated in the innate immune response and inflammatory bowel disease pathways. By repressing the expression of AC007278.2, we clearly found it can regulates the expression of inflammatory and cytokine stimulus response related genes in trans-manner, including CCR7, AZU1, TNIP3, UCN, GNAO1, COL3A1, IL6ST, SKIL, and LIFR. We found AC007278.2 may extensively regulate autoimmunity and the progress of Tfh cell maturation by repressing CCR7 expression. In summary, our study indicated the important regulatory role of lncRNAs in SLE pathogenesis and development, and the novel functions of AC007278.2, which could provide novel biomarkers for SLE diagnosis, treatment and drug screening. Peripheral blood mononuclear cells from SLE patients and normal controls were used for RNA-seq experiment and analysis. Then we used Jurkat cells to knockdown AC007278.2 lncRNA with negative control. RNA-seq experiment was performed for Jurkat cells. Two biological replicates were performed for each experiment.